Detecting Oncogenic Mutations in Whole Blood
|
|
- Jeffry Whitehead
- 5 years ago
- Views:
Transcription
1 WHITE PAPER Detecting Oncogenic Mutations in Whole Blood Analytical validation of Cynvenio Biosystems LiquidBiopsy circulating tumor cell (CTC) capture and next-generation sequencing (NGS) September 2013
2 Overview With the advent of next-generation sequencing (NGS), the pace of discovery in oncology has quickened and the possibilities of precision medicine are rapidly becoming reality. As a more detailed picture of the mutations that drive oncogenesis emerges, new avenues for oncology researchers, clinicians, and drug developers have opened up. However, practical and technical challenges remain that must be overcome to leverage the full potential of NGS and realize the promise of precision medicine. This white paper describes the validation of Cynvenio s LiquidBiopsy system, a precision medicine platform for capture and genetic testing of circulating tumor cells (CTCs) from whole blood. LiquidBiopsy Allows molecular analysis of solid tumors directly from blood Offers the opportunity to capture serial patient samples over time and track disease Delivers sequence data on over 4500 single-nucleotide variants (SNVs) in 50 oncogenes commonly mutated in breast, colon, prostate, and lung tumors Identifies mutations present in as few as 1% of CTCs in a heterogeneous tumor population Can be used to support clinical oncology decision-making, research, and trial management Numerous technical hurdles have up to now prevented routine recovery and sequencing of CTC genomic DNA (see Background, below). These barriers have been overcome with the LiquidBiopsy CLIA-certified services. Here we present data that validates the enumeration and capture of CTCs and resequencing of CTC genomic DNA without whole genome amplification and discuss relevant applications of the technology. 2
3 Background A critical barrier to routine use of NGS in oncology, particularly for solid tumors, is the difficulty of obtaining adequate high-quality DNA (or RNA) template for molecular analysis. Tissue biopsy has several limitations as a potential source of template for sequencing: It is obviously invasive, not always practicable, captures only a small sample of a complex tumor cell population at a single time point, and has little utility for monitoring changes in tumor properties over time or in response to treatment. Preservation of tissue through standard methods, such as formalin-fixed, paraffin-embedded (FFPE) samples, can also create problems for later analysis, including DNA loss and fragmentation (1). Monitoring tumor cells in blood offers an alternative or supplement to tissue biopsy. Although the existence of CTCs and their suspected role in metastasis dates back over a century, only recently has technology advanced to allow routine CTC isolation based on expression of specific cell surface markers for epithelial-derived tumors (EpCAM, CK, and absence of CD45) (2). With the advent of technology able to enumerate CTCs, the prognostic value of CTCs has been validated in several cancers, including breast, colon, and prostate (3-5), demonstrating that CTCs can be used as a relatively noninvasive method to monitor cancer, although studies comparing CTC and primary tumor mutations suggest the degree of concordance may vary with disease and stage (6, e.g.). While CTCs offer a window into tumor status in vivo, they are extremely rare cells, making them difficult to isolate in the quantity and purity required for molecular analysis. The potential clinical importance of rare clones within a tumor cell population for development of drug resistance and metastasis has long been recognized, and there is a growing appreciation of the heterogeneity of tumors in space and time. In this context, in order for genetic analysis to be meaningful, it must be exquisitely sensitive. Robust sequencing data from CTCs requires that they be isolated from non-target cells in sufficient quantity and purity to generate a signal greater than the background of non-target cells that are inevitably carried over into the purified cell fraction. While whole genome amplification can increase the quantity of isolated DNA template, this further degrades the signal-to-noise ratio, and this, until now, has precluded a robust analysis of genetic mutations in isolated CTCs (7). 3
4 Cynvenio Approach In response to the opportunity and challenges described above, Cynvenio has created a patented system called LiquidBiopsy to characterize genetic mutations in CTCs from patient blood samples. As diagrammed in Figure 1, the LiquidBiopsy workflow is composed of three main steps, each supported by custom technology developed at Cynvenio: 1. Blood sample collection - a blood draw is prepared according to package instructions using tubes provided in the LiquidBiopsy Patient Sample kit. The fixed sample is stable for 96 hours without refrigeration, allowing ample time for shipping to Cynvenio s CLIAcertified laboratory. 2. CTC isolation - a proprietary microfluidic platform is used to enumerate and isolate CTCs at high purity using magnetic capture of affinitylabeled cells. 3. Next-generation sequencing - targeted amplification and resequencing to a read depth of 2000-fold is applied to assess over 4500 single-nucleotide variants (SNVs) in 50 oncogenes. As detailed in the Validation section below, LiquidBiopsy is a patented, CLIA-certified service suitable for applications in patient care, research, and clinical trial management and has been shown to: Efficiently capture CTCs at high purity from whole blood Accurately and sensitively detect targeted oncogenic mutations, even those present in just 1% of CTCs Blood sample collection LiquidBiopsy Patient Sample Kit CLIA-certified laboratory service CTC isolation Keep sample stable 96h Patented platform with high yield and high purity Genomic sequencing CLIA-certified 50 genes, >4500 SNVs 1% sensitivity Read depth % False pos. Clinically actionable data Figure 1. LiquidBiopsy workflow 4
5 LiquidBiopsy Validation METHODS Sample collection. Whole blood is drawn and fixed with the LiquidBiopsy fixative (Cynvenio Biosystems, Inc., Westlake Village, CA) within 4 hours of collection according to package instructions. After fixation, blood is shipped to the processing lab using the pre-addressed FedEx shipping material provided in the kit. Samples are stable up to 96 hours after fixation and no dry ice is required for shipping. CTC labeling, enumeration, and recovery. Once the fixed blood sample arrives at Cynvenio s CLIA-certified laboratory, cells are spun out and CTC labeled with a ferrofluid-anti-epcam antibody conjugate. The anti-epcam-labeled CTC are isolated from the mixed population of cells in the total sample using a custom-built LiquidBiopsy microfluidics chip (Figure 2). Additional antibody conjugates can be used for affinity labeling when desired. In the cell spiking experiments, tumor cell lines, e.g. MCF7, were added to normal donor blood prior to fixing. The LiquidBiopsy system employs a three-layer laminar flow chip with PBS in the top compartment, labeled blood sample in the middle, and densityadjusted buffer on the bottom. Following the loading of the sample, cells are permeabilized and labeled in flow conditions with DAPI, pancytokeratin (anti-ck), and anti-cd45 antibodies. The EpCAM +, CK +, CD45 -, DAPI + cells are recovered in a single tube for further molecular analysis using a custom Cynvenio SpinElute tube. Following quality control steps, CTC are enumerated and recovered cells can be returned to the originator or analyzed in the Cynvenio laboratory by NGS, PCR, FISH, or other methods. Figure 2. CTC LiquidBiopsy capture. LiquidBiopsy microfluidic chip captures ferrofluid labeled CTCs (blue) by applying ultra-high magnetic gradients as the sample passes through a custom sheath flow cell. Purified CTCs, free of all but ~0.001% of normal blood cells (red), are readily recovered for further molecular analysis. 5
6 Table 1: CT-Seq 50 oncogene panel (AmpliSeq Panel v2) CT-Seq AmpliSeq Panel v2 ABL1 EZH2 JAK2 PTEN AKT1 FBXW7 JAK3 PTPN11 ALK FGFR1 KDR RB1 APC FGFR2 KIT RET ATM FGFR3 KRAS SMAD4 BRAF FLT3 MET SMARCB1 CDH1 GNA11 MLH1 SMO CDKN2A GNAQ MPL SRC CSF1R GNAS NOTCH1 STK11 CTNNB1 HNF1A NPM1 TP53 EGFR HRAS NRAS VHL ERBB2 IDH1 PDGFRA ERBB4 IDH2 PIK3CA Next-generation sequencing. CT-Seq is a CLIAcertified next-generation sequencing service that allows characterization of SNVs in CTC recovered on the LiquidBiopsy platform without whole genome amplification. DNA is released from the pellet using Cynvenio Digest buffer. Target-specific amplification of genomic DNA is conducted using targeted amplification (Ampliseq v.2 Cancer hot spot panel, Life Technologies) of >4500 mutations in 50 known oncogenes commonly mutated in tumor cells (Table 1). Following library construction, template DNA is sequenced on the Ion Torrent PGM platform (Life/Ion Torrent) to a read depth of 2,000, i.e. 20-fold coverage of a single nucleotide mutation present in 1% of cells. (LiquidBiopsy samples are also compatible with Illumina platforms.) Sensitivity. In validation experiments, tumor cell lines A549, MCF7, HCC1419, and H1975 were added in a defined ratio to non-target cells to determine accuracy and sensitivity of detection of SNVs using CT-Seq. The model tumor cell ratios were based on the published ploidies of eight different mutations contained within the tumor cell genomes: PIK3CA, EGFR, CDKN2A, KRAS, TP53, and STK11. 6
7 % Purity Cell Density (cells/ml) Cell Density (cells/ml) Non-Target cell (c/ml) DETECTING ONCOGENIC MUTATIONS IN WHOLE BLOOD RESULTS Standardized sample collection. Blood samples collected and fixed using the Cynvenio Patient Sample Kit consistently yielded high-quality DNA template for later analysis. This is in contrast FFPE samples, which are not prepared according to a single standardized method, resulting in variable template quality (see discussion in 8, e.g.). CTC Isolation: Efficient cell recovery with high purity. To validate cell recovery using the LiquidBiopsy system under controlled conditions, blood from normal subjects was spiked with the MCF7 tumor cell line, as described in Methods. Recovery of the eluted cells following labeling and separation on the LiquidBiopsy platform was linear at tumor cell densities from 10 to 1,000 cells/ml (Figure 3, top left). Purity of recovered cells pellets was 1-80% and depended on the concentration of tumor cells in the sample (bottom left). On average, fewer than 65 non-target cells/ml were carried over into the eluted cell fraction (top right). This low background allows detection and enumeration of as few as 10 CTC at 1% purity. Interassay variability of target cell recovery was shown to be minimal regardless of instrument or operator (bottom right). CT-Seq: Sensitive and accurate nextgeneration sequencing. Given the speed and low cost per sequencing cycle, we have embraced the Ion Torrent PGM platform. There are some challenges associated with ion detector sequencing. For instance, significant sequencing Linearity of Recovery Non-Target Capture Average < 65 cells/ml Spiked Cell Density (cells/ml) Separate Clinical Samples (N=195) + 2SD - 2SD 100 Linearity of Purity 100 Intra-Assay Variability Spiked Cell Density (cells/ml) Spiked Cell Density (cells/ml) Figure 3. LiquidBiopsy CLIA validation summary. Incremental numbers of tumor cells (MCF7) were added to normal donor blood and 7.5mL aliquots were processed using the Cynvenio protocol. Recovery (top left) and purity (bottom left) were assessed using DAPI, cytokeratin, and CD45 staining to distinguish target (CD45 -, CK +, DAPI + ) from non-target (CD45 +, CK -, DAPI + ) populations. (Top right) Non-target cell capture (EpCAM +,CK -, CD45 +, DAPI + ). (Lower right) Interassay variability across different instruments and operators. 7
8 DETECTING ONCOGENIC MUTATIONS IN WHOLE BLOOD Table 2:! Validation summary Accuracy Precision Linear Range Sensitivity 100% over reportable range 100% over reportable range 0.12% - 50% allele frequency R2 = lower limit of detection 1.0% allele frequency noise is associated with PGM ion detector sequencing contributing high InDel error rate, and sequencing errors associated with strings of homopolymers. In addition, the platform supported Torrent Suite is designed to provide value for common templates either for calling SNPs based upon Mendelian models or for calling SNVs in somatic cancer models. In each case the templates are from samples with abundant amounts of tissue and known tumor representations. For somatic tumor modeling the Torrent Suite does not realistically permit calling below 5% mutation frequency. The Cynvenio CT-Seq test model does not fit in to these descriptors. First and foremost our sample type are cell pellets derived from whole blood. The cellular composition of these pellets is quite heterogenous. We do not use cellular or tumor composition as an predictor of CT-seq mutation frequency. Furthermore the noise associated with PGM sequencing affects our sequencing quality. Consequently we have developed proprietary software solutions to assist us in filtering our sequencing noise including the well known artifacts associated with homologous repeats. By virtue of these solutions and a case controlled approach to sequencing, we have validated our sequencing platform sensitivity to 1% with a false positive rate of zero over our Reportable Range. As summarized in Table 2, experiments with engineered samples spiked with a mixture of wellcharacterized tumor cell lines isolated by LiquidBiopsy (see Methods) demonstrated that CTSeq produces accurate, precise, and robust sequencing results with a sensitivity in the range required for detection of mutations in the small number of CTCs typically recovered from a single blood draw (~120 cells). The test proved exquisitely sensitive, with a lower limit of detection of 0.12% allelic frequency and an average threshold sensitivity of 1%. Resequencing of targeted mutations was 100% accurate and linear across multiplechromosomes, with a regression correlation of R2= over the reportable range from 1% to 50% allele frequency in the engineered cell population (Figure 4). Mutant frequency (%) Figure 4. Linearity of mutant calls across all chromosomes. Sequencing performance and linearity were indexed using a model tumor cell mixture, as described in Methods. Each point (+) is the average mutant frequency detected in triplicate runs for eight different loci Tumor Cell Contribution (%) 8
9 Although sequencing sensitivity was in excess of 0.1%, actual sequencing sensitivity is affected by the clinical sample purity. Routinely, clinical samples have a cell purity that averages 20%. The actual limit of detection of SNVs is determined both by the absolute number of informative cells as well as their purity. Thus the lower limit of detection is approximately 1%. Patient sample results. Results to date with patient samples demonstrate the utility of LiquidBiopsy for applications in precision medicine. Experiments with blood samples from multiple patients with solid tumors of the breast, colon, prostate, or lung have show good recovery of CTC and the ability to detect mutations also found in the corresponding tumor biopsy. Across 236 experiments with four tumor types (prostate, lung, kidney, breast), a standard blood draw of 7.5 ml yielded an average of 120 cells with the expected CTC markers (EpCAM+, CK+, CD45-). The average purity of the recovered cells was 20% CK + cells (8). In one pilot study, CTC isolation and sequencing was performed on patient blood samples taken at different time points to monitor breast cancer markers. Twelve years after a masectomy to remove an ER +, Her2 - tumor, the patient presented with elevated tumor biomarkers but showed no evidence of tumor with a whole body CT scan. Baseline LiquidBiopsy detected two mutations in CTC, including an activating PIK3ca mutation that may predict sensitivity to PIK3ca inhibitors such as everolimus. Two weeks after initiating fulvestrant treatment, CTC number had decreased almost threefold. However, the frequency of PIK3ca mutation had increased by a similar amount (Table 3). These data illustrate how genomic analysis of the CTC population can be applied to detect, characterize, and monitor disease. Table 3: Longitudinal monitoring in breast cancer. Twelve years post-masectomy, a patient presented with elevated tumor biomarkers, but no detectable tumor on body scan. Baseline LiquidBiopsy identified two mutations in circulating CTC. Following treatment with fulvestrant the number of CTC declined, while the frequency of the PIK3ca mutation increased. Sample time CTC count CTC Purity (%) Mutation Baseline % PIK3ca, E542K 12.4% PTPN11, L74F 1.1% 2 weeks post-treatment % PIK3ca, E542K 31.0% Mutant Frequency (%) 9
10 Discussion LiquidBiopsy sequencing of CTC mutations directly from whole blood samples has significant potential to advance oncology on multiple fronts, from patient care, to clinical research, to drug development and clinical trial management. CLINICAL ONCOLOGY AND PATIENT CARE For patient care, the ability to readily obtain tumor sequence from whole blood opens new opportunities to support clinical decision-making with LiquidBiopsy testing. Knowing the mutations present in a patient s tumor can inform initial treatment selection, aid in monitoring the response to treatment, and, should resistance emerge, support selection of a next line of therapy. In cases where no tumor sample is available through biopsy or the tissue quantity is insufficient, LiquidBiopsy offers the potential to recover tumor cells for analysis. This noninvasive method for genomic testing also makes regular high-precision monitoring for recurrence possible, e.g. in breast cancer, where the ability to detect a newly emerging tumor clone early in the metastatic process could allow pre-emptive clinical intervention that otherwise would not be supported. For individuals with a history of breast cancer, LiquidBiopsy is now being offered as a recurrence monitoring service called ClearID Breast Cancer. ClearID Breast Cancer is a two-component testing service that identifies elevated CTC levels in breast cancer survivors (ClearID SCORE). Upon identification of elevated CTC levels, patient samples are sequenced for SNVs associated with breast cancer (ClearID SEQ). ClearID Breast Cancer offers clinicians monitoring breast cancer survivors a simple, non-invasive blood test where disease-linked mutations can trigger more vigilant monitoring than existing standard of care. RESEARCH AND CLINICAL TRIAL MANAGEMENT LiquidBiopsy services also have many potential applications in oncology research, drug development, and clinical trial management. Blood samples from subjects can be drawn and the CTC immediately analyzed or banked for later analysis. The simplicity of sample collection and the ability to bank samples makes the technology readily adaptable to multi-country clinical trials. Because of the sensitivity of the genetic sequencing test, resistant or responsive clones within a tumor are accessible even if they occur at a frequency of 1% in the blood. Therefore, LiquidBiopsy sequencing results could offer early surrogate readout of treatment response, help identify clinically relevant patient sub-populations, and enable adaptive clinical trials, and ultimately, the development of highly tumor-specific therapies. 10
11 Summary Cynvenio received CLIA certification for its LiquidBiopsy services after successfully validating the test s ability to: 1. Recover CTC with high efficiency and purity from a simple blood draw 2. Accurately identify over 4500 mutations (SNVs) in 50 oncogenes with sensitivity down to 1% allelic frequency LiquidBiopsy is the first technology to demonstrate accurate and sensitive detection of rare mutations in CTC isolated from whole blood without whole genome amplification. This technology will be a valuable tool in the clinic, laboratory, and industry in on-going efforts to advance precision medicine. References 1. Pinard R, et al. Assessment of whole genome amplification-induced bias through high-throughput, massively parallel whole genome sequencing. BMC Genomics 2006; 7: Allard WJ, et al. Tumor cells circulate in the peripheral blood of all major carcinomas but not in healthy subjects or patients with nonmalignant diseases. Clin Cancer Res 2004; 10: Cristofanilli M, et al. Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med 2004; 351: Danila, DC, et al. Circulating tumor cell number and prognosis in progressive castration-resistant prostate cancer. Clin Cancer Res 2007: 13: Cohen, SJ, et al. Relationship of circulating tumor cells to tumor response, progression-free survival, and overall survival in patients with metastatic colorectal cancer. J Clin Oncology 2008; 26: Powell AA, et al. Single cell profiling of circulating tumor cells: transcriptional heterogeneity and diversity from breast cancer cell lines. PLoS One 2012; 7(5):e Strauss WM, et al. Rare cell analysis without whole genome amplification by massively parallel sequencing. Cynvenio Biosystems, Inc. white paper. 8. Kotoula V, et al. PloS One 2009; 4(11):e Data on file,, Westlake Village, CA, USA Cynvenio Cynvenio Biosystems, Biosystems, Inc. Inc. (805)
Fluxion Biosciences and Swift Biosciences Somatic variant detection from liquid biopsy samples using targeted NGS
APPLICATION NOTE Fluxion Biosciences and Swift Biosciences OVERVIEW This application note describes a robust method for detecting somatic mutations from liquid biopsy samples by combining circulating tumor
More informationGenomic Medicine: What every pathologist needs to know
Genomic Medicine: What every pathologist needs to know Stephen P. Ethier, Ph.D. Professor, Department of Pathology and Laboratory Medicine, MUSC Director, MUSC Center for Genomic Medicine Genomics and
More informationAccel-Amplicon Panels
Accel-Amplicon Panels Amplicon sequencing has emerged as a reliable, cost-effective method for ultra-deep targeted sequencing. This highly adaptable approach is especially applicable for in-depth interrogation
More informationIntelliGENSM. Integrated Oncology is making next generation sequencing faster and more accessible to the oncology community.
IntelliGENSM Integrated Oncology is making next generation sequencing faster and more accessible to the oncology community. NGS TRANSFORMS GENOMIC TESTING Background Cancers may emerge as a result of somatically
More informationDr David Guttery Senior PDRA Dept. of Cancer Studies and CRUK Leicester Centre University of Leicester
Dr David Guttery Senior PDRA Dept. of Cancer Studies and CRUK Leicester Centre University of Leicester dsg6@le.ac.uk CFDNA/CTDNA Circulating-free AS A LIQUID DNA BIOPSY (cfdna) Tumour Biopsy Liquid Biopsy
More informationPredictive biomarker profiling of > 1,900 sarcomas: Identification of potential novel treatment modalities
Predictive biomarker profiling of > 1,900 sarcomas: Identification of potential novel treatment modalities Sujana Movva 1, Wenhsiang Wen 2, Wangjuh Chen 2, Sherri Z. Millis 2, Margaret von Mehren 1, Zoran
More informationThe Center for PERSONALIZED DIAGNOSTICS
The Center for PERSONALIZED DIAGNOSTICS Precision Diagnostics for Personalized Medicine A joint initiative between The Department of Pathology and Laboratory Medicine & The Abramson Cancer Center The (CPD)
More informationSureSelect Cancer All-In-One Custom and Catalog NGS Assays
SureSelect Cancer All-In-One Custom and Catalog NGS Assays Detect all cancer-relevant variants in a single SureSelect assay SNV Indel TL SNV Indel TL Single DNA input Single AIO assay Single data analysis
More informationAVENIO family of NGS oncology assays ctdna and Tumor Tissue Analysis Kits
AVENIO family of NGS oncology assays ctdna and Tumor Tissue Analysis Kits Accelerating clinical research Next-generation sequencing (NGS) has the ability to interrogate many different genes and detect
More informationFrequency(%) KRAS G12 KRAS G13 KRAS A146 KRAS Q61 KRAS K117N PIK3CA H1047 PIK3CA E545 PIK3CA E542K PIK3CA Q546. EGFR exon19 NFS-indel EGFR L858R
Frequency(%) 1 a b ALK FS-indel ALK R1Q HRAS Q61R HRAS G13R IDH R17K IDH R14Q MET exon14 SS-indel KIT D8Y KIT L76P KIT exon11 NFS-indel SMAD4 R361 IDH1 R13 CTNNB1 S37 CTNNB1 S4 AKT1 E17K ERBB D769H ERBB
More informationTargeted Agent and Profiling Utilization Registry (TAPUR ) Study. February 2018
Targeted Agent and Profiling Utilization Registry (TAPUR ) Study February 2018 Precision Medicine Therapies designed to target the molecular alteration that aids cancer development 30 TARGET gene alterations
More informationNext generation histopathological diagnosis for precision medicine in solid cancers
Next generation histopathological diagnosis for precision medicine in solid cancers from genomics to clinical application Aldo Scarpa ARC-NET Applied Research on Cancer Department of Pathology and Diagnostics
More informationPersonalised cancer care Information for Medical Specialists. A new way to unlock treatment options for your patients
Personalised cancer care Information for Medical Specialists A new way to unlock treatment options for your patients Contents Optimised for clinical benefit 4 Development history 4 Full FIND IT panel vs
More informationEnabling Personalized
Molecular Enabling Personalized Diagnostics Medicine- Targeted Sequencing: NGS-based solutions Silvia Dorn Roel Reinders- Andreas Diplas Friday, 19.06.2015 Company Overview Founded in April 2011 Development
More informationClinical Grade Genomic Profiling: The Time Has Come
Clinical Grade Genomic Profiling: The Time Has Come Gary Palmer, MD, JD, MBA, MPH Senior Vice President, Medical Affairs Foundation Medicine, Inc. Oct. 22, 2013 1 Why We Are Here A Shared Vision At Foundation
More informationA complete next-generation sequencing workfl ow for circulating cell-free DNA isolation and analysis
APPLICATION NOTE Cell-Free DNA Isolation Kit A complete next-generation sequencing workfl ow for circulating cell-free DNA isolation and analysis Abstract Circulating cell-free DNA (cfdna) has been shown
More informationAVENIO ctdna Analysis Kits The complete NGS liquid biopsy solution EMPOWER YOUR LAB
Analysis Kits The complete NGS liquid biopsy solution EMPOWER YOUR LAB Analysis Kits Next-generation performance in liquid biopsies 2 Accelerating clinical research From liquid biopsy to next-generation
More informationTargeted Molecular Diagnostics for Targeted Therapies in Hematological Disorders
Targeted Molecular Diagnostics for Targeted Therapies in Hematological Disorders Richard D. Press, MD, PhD Dept of Pathology Knight Cancer Institute Knight Diagnostic Labs Oregon Health & Science University
More informationLiquid biopsy: the experience of real life case studies
Liquid biopsy: the experience of real life case studies 10 th September 2018 Beatriz Bellosillo Servicio de Anatomía Patológica Hospital del Mar, Barcelona Agenda Introduction Experience in colorectal
More informationIllumina s Cancer Research Portfolio and Dedicated Workflows
Illumina s Cancer Research Portfolio and Dedicated Workflows Michael Sohn Clinical Sales Specialist Spain&Italy 2017 2017 Illumina, Inc. All rights reserved. Illumina, 24sure, BaseSpace, BeadArray, BlueFish,
More informationEBUS-TBNA Diagnosis and Staging of Lung Cancer
EBUS-TBNA Diagnosis and Staging of Lung Cancer Nirag Jhala MD, MIAC Professor of Pathology and Lab Med. Director of Anatomic Pathology and Cytopathology Lewis Katz School of Medicine@ Temple University
More informationNGS in tissue and liquid biopsy
NGS in tissue and liquid biopsy Ana Vivancos, PhD Referencias So, why NGS in the clinics? 2000 Sanger Sequencing (1977-) 2016 NGS (2006-) ABIPrism (Applied Biosystems) Up to 2304 per day (96 sequences
More informationDisclosure. Summary. Circulating DNA and NGS technology 3/27/2017. Disclosure of Relevant Financial Relationships. JS Reis-Filho, MD, PhD, FRCPath
Circulating DNA and NGS technology JS Reis-Filho, MD, PhD, FRCPath Director of Experimental Pathology, Department of Pathology Affiliate Member, Human Oncology and Pathogenesis Program Disclosure of Relevant
More informationNational Surgical Adjuvant Breast and Bowel Project (NSABP) Foundation Annual Progress Report: 2011 Formula Grant
National Surgical Adjuvant Breast and Bowel Project (NSABP) Foundation Annual Progress Report: 2011 Formula Grant Reporting Period July 1, 2012 June 30, 2013 Formula Grant Overview The NSABP Foundation
More informationIllumina Trusight Myeloid Panel validation A R FHAN R A FIQ
Illumina Trusight Myeloid Panel validation A R FHAN R A FIQ G E NETIC T E CHNOLOGIST MEDICAL G E NETICS, CARDIFF To Cover Background to the project Choice of panel Validation process Genes on panel, Protocol
More informationNeoTYPE Cancer Profiles
NeoTYPE Cancer Profiles Multimethod Analysis of 25+ Hematologic Diseases and Solid Tumors Anatomic Pathology FISH Molecular The next generation of diagnostic, prognostic, and therapeutic assessment NeoTYPE
More informationNext Generation Sequencing in Clinical Practice: Impact on Therapeutic Decision Making
Next Generation Sequencing in Clinical Practice: Impact on Therapeutic Decision Making November 20, 2014 Capturing Value in Next Generation Sequencing Symposium Douglas Johnson MD, MSCI Vanderbilt-Ingram
More informationBest of ASCO 2014 Sarcoma
Best of ASCO 2014 Sarcoma Robin L Jones Seattle Cancer Care Alliance University of Washington Fred Hutchinson Cancer Research Center Presentation Outline Overview progress made in sarcoma Highlight 2 trials
More informationPlasma-Seq conducted with blood from male individuals without cancer.
Supplementary Figures Supplementary Figure 1 Plasma-Seq conducted with blood from male individuals without cancer. Copy number patterns established from plasma samples of male individuals without cancer
More informationNext generation diagnostics Bringing high-throughput sequencing into clinical application
Next generation diagnostics Bringing high-throughput sequencing into clinical application Leonardo A. Meza-Zepeda, PhD Translational Genomics Group Institute for Cancer Research Leonardo.Meza-Zepeda@rr-research.no
More informationJennifer Hauenstein Oncology Cytogenetics Emory University Hospital Atlanta, GA
Comparison of Genomic Coverage using Affymetrix OncoScan Array and Illumina TruSight Tumor 170 NGS Panel for Detection of Copy Number Abnormalities in Clinical GBM Specimens Jennifer Hauenstein Oncology
More informationAPPLICATIONS OF NEXT GENERATION SEQUENCING IN SOLID TUMORS - PATHOLOGIST PROSPECTIVE
AMP COMPANION MEETING SYMPOSIUM AT USCAP 2015 NEXT-GENERATION OF PATHOLOGY: ROLE OF PATHOLOGIST IN NGS-BASED PERSONALIZED MEDICINE APPLICATIONS OF NEXT GENERATION SEQUENCING IN SOLID TUMORS - PATHOLOGIST
More informationMEDICAL POLICY Genetic Testing for Breast and Ovarian Cancers
POLICY: PG0067 ORIGINAL EFFECTIVE: 07/30/02 LAST REVIEW: 01/25/18 MEDICAL POLICY Genetic Testing for Breast and Ovarian Cancers GUIDELINES This policy does not certify benefits or authorization of benefits,
More informationPlease Silence Your Cell Phones. Thank You
Please Silence Your Cell Phones Thank You Utility of NGS and Comprehensive Genomic Profiling in Hematopathology Practice Maria E. Arcila M.D. Memorial Sloan Kettering Cancer Center New York, NY Disclosure
More informationLa biopsia liquida. Aldo Scarpa. Anatomia Patologica e ARC-NET Centro di Ricerca Applicata sul Cancro
La biopsia liquida Aldo Scarpa Anatomia Patologica e ARC-NET Centro di Ricerca Applicata sul Cancro Azienda Ospedaliera Universitaria Integrata di Verona Obstacles to precision oncology Genomic heterogeneity
More informationSecuenciación masiva: papel en la toma de decisiones
Secuenciación masiva: papel en la toma de decisiones Cancer is a Genetic Disease Development of cancer is driven by the acquisition of somatic genetic alterations: Nonsynonymous point mutations: missense.
More informationDr Yvonne Wallis Consultant Clinical Scientist West Midlands Regional Genetics Laboratory
Dr Yvonne Wallis Consultant Clinical Scientist West Midlands Regional Genetics Laboratory Personalised Therapy/Precision Medicine Selection of a therapeutic drug based on the presence or absence of a specific
More informationADRL Advanced Diagnostics Research Laboratory
ADRL Advanced Diagnostics Research Laboratory John DeCoteau, MD FRCP Department of Pathology, Division of Hematopathology University of Saskatchewan Saskatchewan Cancer Agency ADRL Project Objectives New
More informationClinical Grade Biomarkers in the Genomic Era Observations & Challenges
Clinical Grade Biomarkers in the Genomic Era Observations & Challenges IOM Committee on Policy Issues in the Clinical Development & Use of Biomarkers for Molecularly Targeted Therapies March 31-April 1,
More informationPerformance Characteristics BRCA MASTR Plus Dx
Performance Characteristics BRCA MASTR Plus Dx with drmid Dx for Illumina NGS systems Manufacturer Multiplicom N.V. Galileïlaan 18 2845 Niel Belgium Table of Contents 1. Workflow... 4 2. Performance Characteristics
More informationEXAMPLE. - Potentially responsive to PI3K/mTOR and MEK combination therapy or mtor/mek and PKC combination therapy. ratio (%)
Dr Kate Goodhealth Goodhealth Medical Clinic 123 Address Road SUBURBTOWN NSW 2000 Melanie Citizen Referring Doctor Your ref Address Dr John Medico 123 Main Street, SUBURBTOWN NSW 2000 Phone 02 9999 9999
More informationDiagnostic application of SNParrays to brain cancers
Diagnostic application of SNParrays to brain cancers Adriana Olar 4/17/2018 No disclosures 55 yo M, focal motor seizure T2 T1-post C DIAGNOSIS BRAIN, LEFT FRONTAL LOBE, BIOPSY: - DIFFUSE GLIOMA, OLIGODENDROGLIAL
More informationTransform genomic data into real-life results
CLINICAL SUMMARY Transform genomic data into real-life results Biomarker testing and targeted therapies can drive improved outcomes in clinical practice New FDA-Approved Broad Companion Diagnostic for
More informationCTC in clinical studies: Latest reports on GI cancers
CTC in clinical studies: Latest reports on GI cancers François-Clément Bidard, MD PhD GI cancers are characterized by Multimodal treatment strategies Treatments are adapted to tumor burden & prognosis
More informationNeoTYPE Cancer Profiles
NeoTYPE Cancer Profiles 30+ Multimethod Assays for Hematologic Diseases and Solid Tumors Molecular FISH Anatomic Pathology The next generation of diagnostic, prognostic, and therapeutic assessment What
More informationIdentification and clinical detection of genetic alterations of pre-neoplastic lesions Time for the PML ome? David Sidransky MD Johns Hopkins
Identification and clinical detection of genetic alterations of pre-neoplastic lesions Time for the PML ome? David Sidransky MD Johns Hopkins February 3-5, 2016 Lansdowne Resort, Leesburg, VA Molecular
More informationAgenda. What is a Liquid Biopsy? Biocept technology. Concordance With Tissue. Clinical Applications. Billing and Reimbursement.
Agenda What is a Liquid Biopsy? Biocept technology Concordance With Tissue Clinical Applications Billing and Reimbursement Recap & Questions 1 Targets of Tumor Found in Liquid Biopsy 1 Eric Topol, Professor
More informationTargeted next-generation sequencing of 50 cancer-related genes in Japanese patients with oral squamous cell carcinoma
Original Article Targeted next-generation sequencing of 50 cancer-related genes in Japanese patients with oral squamous cell carcinoma Tumor Biology September 2018: 1 9 Ó The Author(s) 2018 Article reuse
More informationCell-free tumor DNA for cancer monitoring
Learning objectives Cell-free tumor DNA for cancer monitoring Christina Lockwood, PhD, DABCC, DABMGG Department of Laboratory Medicine 1. Define circulating, cell-free tumor DNA (ctdna) 2. Understand the
More informationDevelopment of Circulating Tumor DNA
Development of Circulating Tumor DNA Title of presentation Arial Bold 30pt in White Biomarkers Secondary title 22pt using Arial Next in White Generation Sequencing Brian Dougherty PhD, MBA Translational
More informationAD (Leave blank) TITLE: Genomic Characterization of Brain Metastasis in Non-Small Cell Lung Cancer Patients
AD (Leave blank) Award Number: W81XWH-12-1-0444 TITLE: Genomic Characterization of Brain Metastasis in Non-Small Cell Lung Cancer Patients PRINCIPAL INVESTIGATOR: Mark A. Watson, MD PhD CONTRACTING ORGANIZATION:
More informationProspective Clinical Study of Circulating Tumor Cells For Colorectal Cancer Screening
Prospective Clinical Study of Circulating Tumor Cells For Colorectal Cancer Screening Results From a Multi-Year 620-Sample Study CRC: SLOW GROWING, PREVENTABLE POLYP TO CANCER CAN TAKE 5 TO 15 YEARS CANCER
More informationThe Next Generation in Cancer Diagnostics.
The Next Generation in Cancer Diagnostics. OncoTarget was created specifically for cancer patients. Every patient s cancer is unique, which is why discovering what makes it unique can be essential for
More informationChallenges for use of CTCs as a Diagnostic. Farideh Z. Bischoff, Ph.D. Interim CSO Sr. Director, Translational Clinical Development Biocept, Inc.
Challenges for use of CTCs as a Diagnostic Farideh Z. ischoff, Ph.D. Interim CSO Sr. Director, Translational Clinical Development iocept, Inc. Current Technology for CTC Testing Existing CTC testing platform
More informationCirculating tumour DNA in breast cancer. Kathleen Burke, PhD Bioinformatics Postdoctoral Fellow Laboratory of Dr. Jorge Reis-Filho
Circulating tumour DNA in breast cancer Kathleen Burke, PhD Bioinformatics Postdoctoral Fellow Laboratory of Dr. Jorge Reis-Filho Conflicts of Interest I have no financial relationships to disclose I will
More informationLiquid biopsy in lung cancer: The EGFR paradigm
Liquid biopsy in lung cancer: The EGFR paradigm Lynette M. Sholl, M.D. Brigham and Women s Hospital Dana Farber Cancer Institute Department of Pathology Boston, MA Disclosure of Relevant Financial Relationships
More informationMEDICAL POLICY. SUBJECT: MOLECULAR PANEL TESTING OF CANCERS TO IDENTIFY TARGETED THERAPIES (Excluding NSCLC and CRC) EFFECTIVE DATE: 12/21/17
MEDICAL POLICY SUBJECT: MOLECULAR PANEL TESTING OF PAGE: 1 OF: 5 If a product excludes coverage for a service, it is not covered, and medical policy criteria do not apply. If a commercial product, including
More informationNGS IN ONCOLOGY: FDA S PERSPECTIVE
NGS IN ONCOLOGY: FDA S PERSPECTIVE ASQ Biomed/Biotech SIG Event April 26, 2018 Gaithersburg, MD You Li, Ph.D. Division of Molecular Genetics and Pathology Food and Drug Administration (FDA) Center for
More informationStrandAdvantage Tissue-Specific Cancer Genomic Tests. Empowering Crucial First-Line Therapy Decisions for Your Patient
StrandAdvantage Tissue-Specific Cancer Genomic Tests Empowering Crucial First-Line Therapy Decisions for Your Patient Harness the power of precision medicine with StrandAdvantage Precision medicine in
More informationSelect analysis on the next pages. Sample request and sending address see last page. Institut für Pathologie und Molekularpathologie
Diagnostic Tumor Genome Analysis Schmelzbergstrasse 12 8091 Zürich Tel.: (+41) 044 255 3929 Fax.: (+41) 044 255 4416 Client (address, telephone number): ngs.pathologie@usz.ch www.pathologie.usz.ch Sample-Nr:
More informationProtein Domain-Centric Approach to Study Cancer Somatic Mutations from High-throughput Sequencing Studies
Protein Domain-Centric Approach to Study Cancer Somatic Mutations from High-throughput Sequencing Studies Dr. Maricel G. Kann Assistant Professor Dept of Biological Sciences UMBC 2 The term protein domain
More informationClick to edit Master /tle style
Click to edit Master /tle style Tel: (314) 747-7337 Toll Free: (866) 450-7697 Fax: (314) 747-7336 Email: gps@wustl.edu Website: gps.wustl.edu GENETIC TESTING IN CANCER Ka/nka Vigh-Conrad, PhD Genomics
More informationDigitizing the Proteomes From Big Tissue Biobanks
Digitizing the Proteomes From Big Tissue Biobanks Analyzing 24 Proteomes Per Day by Microflow SWATH Acquisition and Spectronaut Pulsar Analysis Jan Muntel 1, Nick Morrice 2, Roland M. Bruderer 1, Lukas
More informationOut-Patient Billing CPT Codes
Out-Patient Billing CPT Codes Updated Date: August 3, 08 Client Billed Molecular Tests HPV DNA Tissue Testing 8764 No Medicare Billed - Molecular Tests NeoARRAY NeoARRAY SNP/Cytogenetic No 89 NeoLAB NeoLAB
More informationYoungnam Cho. National Cancer Center Biomarker Branch
Youngnam Cho National Cancer Center Biomarker Branch Contents 1. Liquid Biopsy 2. Circulating Tumor Cells from Blood 3. Cell-free DNA from Blood 1. Liquid biopsy Cancer Diagnosis IMAGING TISSUE BIOPSY
More informationClinical, Pathologic and Molecular Updates
Colorectal Cancer: Clinical, Pathologic and Molecular Updates Joanna A. Gibson, M.D./Ph.D. Yale University School of Medicine/Yale New Haven Hospital, Department of Pathology Gastrointestinal, Pancreaticobiliary
More informationPrior Authorization. Additional Information:
Genetic Testing for Cowden Syndrome - PTEN Gene MP9488 Covered Service: Prior Authorization Required: Additional Information: Yes when meets criteria below Yes as shown below Pre and post-test genetic
More informationExpressArt FFPE Clear RNAready kit
Features and Example Results General problems with FFPE samples Formalin-fixation of tissues results in severe RNA fragmentation, as well as in RNA RNA, RNA-DNA and RNA protein cross-linking, which impairs
More informationPatricia Aoun MD, MPH Professor and Vice-Chair for Clinical Affairs Medical Director, Clinical Laboratories Department of Pathology City of Hope
Patricia Aoun MD, MPH Professor and Vice-Chair for Clinical Affairs Medical Director, Clinical Laboratories Department of Pathology City of Hope National Medical Center Disclosures I have no disclosures
More informationQué hemos aprendido hasta hoy? What have we learned so far?
Qué hemos aprendido hasta hoy? What have we learned so far? Luís Costa Hospital de Santa Maria & Instituto de Medicina Molecular Faculdade de Medicina de Lisboa Disclosures Research Grants: Amgen; Novartis;
More informationComprehensive Genomic Profiling, in record time. Accurate. Clinically Proven. Fast.
Comprehensive Genomic Profiling, in record time Accurate. ly Proven. Fast. PCDx advantages Comprehensive genomic profiling, in record time PCDx Comprehensive Genomic Profiling (CGP) provides precise information
More informationIntroduction of an NGS gene panel into the Haemato-Oncology MPN service
Introduction of an NGS gene panel into the Haemato-Oncology MPN service Dr. Anna Skowronska, Dr Jane Bryon, Dr Samuel Clokie, Dr Yvonne Wallis and Professor Mike Griffiths West Midlands Regional Genetics
More informationDetection of aneuploidy in a single cell using the Ion ReproSeq PGS View Kit
APPLICATION NOTE Ion PGM System Detection of aneuploidy in a single cell using the Ion ReproSeq PGS View Kit Key findings The Ion PGM System, in concert with the Ion ReproSeq PGS View Kit and Ion Reporter
More informationNature Methods: doi: /nmeth Supplementary Figure 1
Supplementary Figure 1 Finite-element analysis of cell cluster dynamics in different cluster trap architectures. (a) Cluster-Chip (b) Filter (c) A structure identical to the Cluster-Chip except that one
More informationNGS ONCOPANELS: FDA S PERSPECTIVE
NGS ONCOPANELS: FDA S PERSPECTIVE CBA Workshop: Biomarker and Application in Drug Development August 11, 2018 Rockville, MD You Li, Ph.D. Division of Molecular Genetics and Pathology Food and Drug Administration
More informationPathologists role Ancillary Studies in Cytology Challenges. Pre-analytical issues. LUNG CYTOLOGY Predictive markers and molecular tests
Pathologists role LUNG CYTOLOGY Predictive markers and molecular tests Prof. Fernando Schmitt Department of Pathology and Oncology, Medical Faculty of Porto University Head of Pathology Unit, IPATIMUP
More informationSimple, rapid, and reliable RNA sequencing
Simple, rapid, and reliable RNA sequencing RNA sequencing applications RNA sequencing provides fundamental insights into how genomes are organized and regulated, giving us valuable information about the
More informationCharacterisation of structural variation in breast. cancer genomes using paired-end sequencing on. the Illumina Genome Analyser
Characterisation of structural variation in breast cancer genomes using paired-end sequencing on the Illumina Genome Analyser Phil Stephens Cancer Genome Project Why is it important to study cancer? Why
More informationHigh Sensitivity Immunomagnetic CTC Isolation as Compared to Alternative Isolation Methods
High Sensitivity Immunomagnetic CTC Isolation as Compared to Alternative Isolation Methods 1. Introduction: An overview of CTC isolation methods 2. Challenges for direct comparisons of CTC recovery 3.
More informationNon-Profit Startup Paradigm Launches Cancer Panel Based on DNA, RNA Sequencing
Non-Profit Startup Paradigm Launches Cancer Panel Based on DNA, RNA Sequencing April 11, 2014 By Tony Fong Non-profit diagnostics outfit Paradigm last month joined a growing list of entrants in the clinical
More informationValidation of QClamp as Next Generation Liquid Biopsy Technique for Colorectal Cancer He James Zhu M.D. Ph.D
Validation of QClamp as Next Generation Liquid Biopsy Technique for Colorectal Cancer He James Zhu M.D. Ph.D Department of Radiation Oncology University of Florida College of Medicine Outline Objective
More informationSimpler QC for your Quality Systems. Thermo Scientific AcroMetrix Molecular Standards and Quality Controls. North American version
Simpler QC for your Quality Systems Thermo Scientific AcroMetrix Molecular Standards and Quality Controls North American version AcroMetrix Contents Introduction 4 Superior QC: AcroMetrix molecular quality
More informationFAQs for UK Pathology Departments
FAQs for UK Pathology Departments This is an educational piece written for Healthcare Professionals FAQs for UK Pathology Departments If you would like to discuss any of the listed FAQs further, or have
More informationComprehensive Analyses of Circulating Cell- Free Tumor DNA
Comprehensive Analyses of Circulating Cell- Free Tumor DNA Boston, MA June 28th, 2016 Derek Murphy, Ph.D. Scientist, Research and Development Personal Genome Diagnostics Acquisition of Somatic Alterations
More informationDNA-seq Bioinformatics Analysis: Copy Number Variation
DNA-seq Bioinformatics Analysis: Copy Number Variation Elodie Girard elodie.girard@curie.fr U900 institut Curie, INSERM, Mines ParisTech, PSL Research University Paris, France NGS Applications 5C HiC DNA-seq
More informationWhat is the status of the technologies of "precision medicine?
Session 2: What is the status of the technologies of "precision medicine? Gideon Blumenthal, MD, Clinical Team Leader, Thoracic and Head/Neck Oncology, Center for Drug Evaluation and Research (CDER), U.S.
More informationNew Drug development and Personalized Therapy in The Era of Molecular Medicine
New Drug development and Personalized Therapy in The Era of Molecular Medicine Ramesh K. Ramanathan MD Virginia G. Piper Cancer Center Translational Genomics Research Institute Scottsdale, AZ Clinical
More informationMetastatic Hepatic Angiosarcoma and BRAF Inhibitor Therapy
Case Series imedpub Journals www.imedpub.com Journal of Clinical Epigenetics DOI: 10.21767/2472-1158.100085 Abstract Metastatic Hepatic Angiosarcoma and BRAF Inhibitor Therapy Context: BRAF mutations lead
More informationECMC cfdna consensus meeting
ECMC cfdna consensus meeting State of the art for cfdna technologies 24 th November 2014 Applications of ctdna analysis for drug development Potential of ctdna analysis to: Identify the right patients
More informationA Novel CTC-Detecting Technique Using TelomeScan and Its Clinical Applications
A Novel CTC-Detecting Technique Using TelomeScan and Its Clinical Applications Yasuo Urata CEO and President Oncolys BioPharma Inc. February 16, 2013 Telomere Length is a Limiting Factor for Cell Replication
More informationMolecular Testing Updates. Karen Rasmussen, PhD, FACMG Clinical Molecular Genetics Spectrum Medical Group, Pathology Division Portland, Maine
Molecular Testing Updates Karen Rasmussen, PhD, FACMG Clinical Molecular Genetics Spectrum Medical Group, Pathology Division Portland, Maine Keeping Up with Predictive Molecular Testing in Oncology: Technical
More informationMolecular. Oncology & Pathology. Diagnostic, Prognostic, Therapeutic, and Predisposition Tests in Precision Medicine. Liquid Biopsy.
Molecular Oncology & Pathology Hereditary Cancer Somatic Cancer Liquid Biopsy Next-Gen Sequencing qpcr Sanger Sequencing Diagnostic, Prognostic, Therapeutic, and Predisposition Tests in Precision Medicine
More informationAn ultrasensitive method for quantitating circulating tumor DNA with broad patient coverage
An ultrasensitive method for quantitating circulating tumor DNA with broad patient coverage Aaron M Newman1,2,7, Scott V Bratman1,3,7, Jacqueline To3, Jacob F Wynne3, Neville C W Eclov3, Leslie A Modlin3,
More informationSUPPLEMENTARY INFORMATION
SUPPLEMENTARY INFORMATION Systematic investigation of cancer-associated somatic point mutations in SNP databases HyunChul Jung 1,2, Thomas Bleazard 3, Jongkeun Lee 1 and Dongwan Hong 1 1. Cancer Genomics
More informationIMPLEMENTING NEXT GENERATION SEQUENCING IN A PATHOLOGY LABORATORY
Madrid, Spain IMPLEMENTING NEXT GENERATION SEQUENCING IN A PATHOLOGY LABORATORY Dr. JL Rodríguez Peralto NGS Ion Torrent Oncomine Focus Assay - Implementation experience for EGFR mutation detection
More informationAnalysis of Massively Parallel Sequencing Data Application of Illumina Sequencing to the Genetics of Human Cancers
Analysis of Massively Parallel Sequencing Data Application of Illumina Sequencing to the Genetics of Human Cancers Gordon Blackshields Senior Bioinformatician Source BioScience 1 To Cancer Genetics Studies
More informationSupplementary Figure 1
Supplementary Figure 1 Supplementary Fig. 1: Quality assessment of formalin-fixed paraffin-embedded (FFPE)-derived DNA and nuclei. (a) Multiplex PCR analysis of unrepaired and repaired bulk FFPE gdna from
More informationKarl Kashofer, Phd Institut für Pathologie Medizinische Universität Graz
Expanding on WHO guideline compliant molecular testing of central nervous system tumors by low density whole genome sequencing. Karl Kashofer, Phd Institut für Pathologie Medizinische Universität Graz
More informationLaboratory Service Report
Client C7028846-DLP Rochester Rochester, N 55901 Specimen Type Peripheral blood CR PDF Report available at: https://test.mmlaccess.com/reports/c7028846-zwselwql7p.ashx Indication for Test DS CR Pathogenic
More information