Characterisation of structural variation in breast. cancer genomes using paired-end sequencing on. the Illumina Genome Analyser
|
|
|
- Corey Jesse Harrell
- 5 years ago
- Views:
Transcription
1 Characterisation of structural variation in breast cancer genomes using paired-end sequencing on the Illumina Genome Analyser Phil Stephens Cancer Genome Project
2 Why is it important to study cancer?
3 Why is it important to study cancer? Causes of cancer How cancers develop Pathways involved
4 Why is it important to study cancer? Causes of cancer How cancers develop Pathways involved Development of tests for early detection
5 Why is it important to study cancer? Causes of cancer How cancers develop Pathways involved Development of tests for early detection New targets for anticancer drug development
6 Why is it important to study cancer? Causes of cancer How cancers develop Pathways involved Development of tests for early detection New targets for anticancer drug development Monitor whether treatment is working
7 Why is it important to study cancer? Causes of cancer How cancers develop Pathways involved Development of tests for early detection New targets for anticancer drug development Monitor whether treatment is working Personalised treatment of cancer
8 Why is it important to study cancer? Causes of cancer How cancers develop Pathways involved Development of tests for early detection New targets for anticancer drug development Monitor whether treatment is working Personalised treatment of cancer
9 Why is it important to study cancer? Causes of cancer How cancers develop Pathways involved Development of tests for early detection New targets for anticancer drug development Monitor whether treatment is working Personalised treatment of cancer
10 Challenges of studying solid tumours
11 Breast cancer spectral karyotype C/O Paul Edwards, Departments of Pathology and Oncology, University of Cambridge 73 Chromosomes, 37 structural abnormalities
12 Amplification MYC in Breast Cancer MYC Genomic location (Mb)
13 Point mutations & Indels Pre-cancerous lesion in situ cancer Invasive cancer Metastatic cancer
14 Point mutations & Indels Pre-cancerous lesion in situ cancer Invasive cancer Metastatic cancer ~20 Cancer causing mutations
15 Point mutations & Indels Pre-cancerous lesion in situ cancer Invasive cancer Metastatic cancer ~20 Cancer causing mutations 100,000 Passenger mutations
16 Pessimism around studying solid tumours
17 BRAF is an oncogene 70% of Melanoma T1799A V600E
18 BRAF is an oncogene 70% of Melanoma T1799A V600E BRAF is not important Melanoma
19 BRAF is an oncogene 70% of Melanoma T1799A V600E BRAF is not important Melanoma BRAF is not a good drug target
20 BRAF is an oncogene 70% of Melanoma T1799A V600E BRAF is not important Melanoma BRAF is not a good drug target Melanoma is too complex to treat effectively
21 Patient with malignant melanoma Courtesy of Dr Grant McArthur
22 Selective inhibitor of BRAF V600E (Plexxicon 4032) Courtesy of Dr Grant McArthur
23 Selective inhibitor of BRAF V600E (Plexxicon 4032) Before 15 days after Courtesy of Dr Grant McArthur
24 New sequencing technologies
25 Rearrangement characterisation
26 Summary of Illumina GA protocol 500bps Randomly shear DNA Size select Sequence from & ligate Illumina adaptors & amplify both ends
27 Summary of Illumina GA protocol 400 bps 37 bps 37 bps
28 Summary of Illumina GA protocol 400 bps 37 bps 37 bps Align reads to ref sequence MAQ algorithm Li Heng, Genome Res., Nov 2008
29 Correctly mapping paired end reads 400 bps 37 bps 37 bps Chromosome 11
30 Incorrectly mapping paired-end reads 400 bps 37 bps 37 bps Chromosome 11 Chromosome 8
31 PCR amplify in tumour and matched normal Somatic Germline Artefact T N T N T N
32 PCR amplify in tumour and matched normal Somatic Germline Artefact T N T N T N
33 PCR amplify in tumour and matched normal Somatic Germline Artefact T N T N T N 6 bps of microhomology at break
34 Structural variation screen 9 matched breast cancer cell lines 49.0 Gb total data 8.5 mean physical coverage
35 Illumina GA sequencing:- Broad objectives Structural variation Fusion genes Copy number changes Structure of amplicons
36 Breast cancer HCC38 spectral karyotype C/O Paul Edwards, Departments of Pathology and Oncology, University of Cambridge 73 Chromosomes, 37 structural abnormalities
37 Breast cancer HCC38 (Triple neg) 238 somatic structural variants
38 Breast cancer HCC38 (Triple neg) somatic structural variants Patterns of variation 0
39 What are these structural variants doing?
40 Copy number ~160 kb copy number increase Chromosome 3 position (Mb)
41 Copy number 164 kb tandem duplication T N Chromosome 3 position (Mb)
42 Copy number 164 kb tandem duplication Chromosome 3 position (Mb) SLC26A6/PRKAR2A in frame fusion gene SLC26A6 PRKAR2A (Exons 1-17) (Exons 4-11) 5 UTR 3 UTR
43 Copy number 164 kb tandem duplication Genomic PCR bps T N T N Chromosome 3 position (Mb) SLC26A6/PRKAR2A in frame fusion gene SLC26A6 PRKAR2A (Exons 1-17) (Exons 4-11) 5 UTR 3 UTR
44 Copy number 164 kb tandem duplication Genomic PCR bps T N T N Chromosome 3 position (Mb) SLC26A6/PRKAR2A in frame fusion gene FISH confirmation of tandem duplication SLC26A6 PRKAR2A (Exons 1-17) (Exons 4-11) 5 UTR 3 UTR
45 bps T N RT-PCR
46 bps T N RT-PCR
47 bps T N RT-PCR
48 bps T N RT-PCR Predicted 914 amino acid fusion protein MGLADASGPRDTQALLSATQAMDLRRRDYHMERPLLNQEHLEELGRWGSAPRTHQWRTWLQCSRARAYALLLQHLPVLVWLPRYPVRDWLLGDLLSGL SVAIMQLPQGLAYALLAGLPPVFGLYSSFYPVFIYFLFGTSRHISVGTFAVMSVMVGSVTESLAPQALNDSMINETARDAARVQVASTLSVLVGLFQVGLGLIH FGFVVTYLSEPLVRGYTTAAAVQVFVSQLKYVFGLHLSSHSGPLSLIYTVLEVCWKLPQSKVGTVVTAAVAGVVLVVVKLLNDKLQQQLPMPIPGELLTLIGAT GISYGMGLKHRFEVDVVGNIPAGLVPPVAPNTQLFSKLVGSAFTIAVVGFAIAISLGKIFALRHGYRVDSNQELVALGLSNLIGGIFQCFPVSCSMSRSLVQEST GGNSQVAGAISSLFILLIIVKLGELFHDLPKAVLAAIIIVNLKGMLRQLSDMRSLWKANRADLLIWLVTFTATILLNLDLGLVVAVIFSLLLVVVRTQMPHYSVLGQ VPDTDIYRDVAEYSEAKEVRGVKVFRSSATVYFANAEFYSDALKQRCGVDVDFLISQKKKLLKKQEQLKLKQLQKEEKLRKQAASPKGASVSINVNTSLEDMR SNNVEDCKMVIHPKTDEQRCRLQEACKDILLFKNLDQEQLSQVLDAMFERIVKADEHVIDQGDDGDNFYVIERGTYDILVTKDNQTRSVGQYDNRGSFGEL ALMYNTPRAATIVATSEGSLWGLDRVTFRRIIVKNNAKKRKMFESFIESVPLLKSLEVSERMKIVDVIGEKIYKDGERIITQGEKADSFYIIESGEVSILIRSRTKSN KDGGNQEVEIARCHKGQYFGELALVTNKPRAASAYAVGDVKCLVMDVQAFERLLGPCMDIMKRNISHYEEQLVKMFGSSVDLGNLGQStop
49 Five expressed in frame fusion genes 2 generated by tandem duplications 3 generated by large inversions
50 Very small rearrangements:- below the resolution of copy number graphs
51 Very small rearrangements:- below the resolution of copy number graphs T N 5 kb tandem duplication, spanned by 4 reads TNRC15:- In frame duplication exons 14 & 15
52 Different patterns of structural variation are emerging from other breast cancers
53 Patterns of somatic structural variation HCC38 HCC1937 HCC1954 Triple Neg BRCA1 null ERBB2 Positive
54 Patterns of somatic structural variation HCC38 HCC1937 HCC1954 Triple Neg BRCA1 null ERBB2 Positive
55 Patterns of somatic structural variation HCC38 HCC1937 HCC1954 Triple Neg BRCA1 null ERBB2 Positive
56 Copy number Complex patterns of structural variation Solexa copy number:- chromosome 6
57 Copy number Complex patterns of structural variation Tandem Duplication Solexa copy number:- chromosome 6
58 Copy number Complex patterns of structural variation Tandem Duplication Deletion & Tandem Duplication Solexa copy number:- chromosome 6
59 Copy number Complex patterns of structural variation t(6;7) translocation 10 8 Tandem Duplication t(6;7) translocation Deletion & Tandem Duplication Solexa copy number:- chromosome 6
60 Copy number Complex patterns of structural variation 10 8 t(6;7) translocation Tandem Duplication Inversion & Tandem Duplication & t(6;7) translocation t(6;7) translocation Deletion & Tandem Duplication Solexa copy number:- chromosome 6
61 Copy number Complex patterns of structural variation t(6;7) translocation Tandem Duplication Inversion & Tandem Duplication & t(6;7) translocation Inversion & Tandem Duplication & t(6;7) translocation t(6;7) translocation Deletion & Tandem Duplication Solexa copy number:- chromosome 6
62 Copy number Complex patterns of structural variation t(6;7) translocation Tandem Duplication Complex Complex Inversion & Tandem Duplication & t(6;7) translocation Inversion & Tandem Duplication & t(6;7) translocation t(6;7) translocation Deletion & Tandem Duplication Solexa copy number:- chromosome 6
63 Summary of breast cancer cell line data 9 breast cancer cell lines 1152 somatic rearrangements 16 In-frame fusion genes (15/16 expressed)
64 Structural variation screen on 15 primary breast cancers 2 Luminal A 2 Luminal B 3 Basal like 2 BRCA1 neg 2 BRCA2 neg 3 ERBB2 + 1 Lobular 66.6 Gb total data 7.4 mean physical coverage
65 199 somatic structural variants Triple negative
66 Triple negative somatic structural variants Patterns of variation
67 Triple negative somatic structural variants Patterns of variation
68 ERRB2 positive somatic structural variants Patterns of variation
69 ERRB2 positive somatic structural variants Patterns of variation
70 Luminal B expression somatic structural variants Patterns of variation
71 Invasive lobular carcinoma somatic structural variant Patterns of variation
72 Novel expressed in frame fusion gene
73 Novel expressed in frame fusion gene 16.8 Mb inversion
74 Novel expressed in frame fusion gene 16.8 Mb inversion
75 Novel expressed in frame fusion gene 16.8 Mb inversion
76 Novel expressed in frame fusion gene 16.8 Mb inversion
77 Novel expressed in frame fusion gene 16.8 Mb inversion
78 Novel expressed in frame fusion gene 16.8 Mb inversion
79 Novel expressed in frame fusion gene 16.8 Mb inversion
80 Very small rearrangements T N 3 kb deletion RB1:- Deletion Exon 13
81 Summary of primary breast cancer data 15 primary breast cancers 1014 Somatic rearrangements 10 In-frame fusion genes (5 expressed)
82 How do we identify the driver mutations?
83 How do we identify the driver mutations? 139 genes rearranged in more than one sample
84 How do we identify the driver mutations? 139 genes rearranged in more than one sample 22 gene fusions ~300 primary breast cancers FISH cdna PCR (Jorge Reis-Filho) (John Foekins)
85 Whole exome sequencing (Agilent Sure Select)
86 Whole exome sequencing (Agilent Sure Select) Shear genomic DNA, ligate Illumina adaptors Hybridise to baits that span exons & wash Sequence form both ends
87 Breast cancer samples (28 total) 21 x ER + HER2 6 x ER + HER2 + 3 x triple neg
88 Substitutions in known cancer genes PD3995a AKT1 E17K PD3995a NF1 G-1T PD3994a PIK3CA N345K PD3989a PIK3CA E545K PD3856a PIK3CA H1047R PD3857a PIK3CA H1047R PD3888a PIK3CA H1047R PD3983a PIK3CA H1047R PD3985a PIK3CA H1047R PD3992a PIK3CA H1047R PD3996a PTEN Y27D PD3991a TP53 G245S PD4002a TP53 H179Y PD3987a TP53 Y220C PD3986a TP53 G+1A PD3985a TP53 R306X
89 High confidence Indels Sample Gene Mutation PD3849a CDH1 V193X PD3984a MAP2K4 V151X PD3992a MAP2K4 I81X PD3989a PTEN L370X
90 High confidence Indels Sample Gene Mutation PD3849a CDH1 V193X PD3984a MAP2K4 V151X PD3992a MAP2K4 I81X PD3989a PTEN L370X PD3995a GATA3 N352X PD3988a GATA3 N352X PD4004a GATA3 Read through
91 Novel cancer genes
92 Novel cancer genes Integrating rearrangement and exome data 2 novel pathways deregulated in a large proportion of ER pos breast cancer
93 Potential applications in healthcare
94 Personalised Haematology Risk stratification Therapy duration Prediction of relapse Tumour cells Time (months)
95 Tumour-specific rearrangements
96 Plasma DNA Normal tissues Cancer DNA with tumour-specific mutation
97 Work flow Identify tumour-specific rearrangements from cancer DNA 2 weeks ~ 2,500
98 Work flow Identify tumour-specific rearrangements from cancer DNA 2 weeks ~ 2,500 Design & test quantitative assay for rearrangements 1 week 250
99 Work flow Identify tumour-specific rearrangements from cancer DNA 2 weeks ~ 2,500 Design & test quantitative assay for rearrangements Extract DNA from plasma (10-20mL blood sample) 1 week 250 ½ day 50
100 Work flow Identify tumour-specific rearrangements from cancer DNA 2 weeks ~ 2,500 Design & test quantitative assay for rearrangements Extract DNA from plasma (10-20mL blood sample) 1 week 250 ½ day 50 Quantify tumour DNA ½ day 50
101 Assay design
102 Detecting 1 copy of tumour genome
103 Serial measurements
104 Potential healthcare applications Monitoring tumour response to therapy in real-time Reduce toxicity, prevent drug wastage
105 Potential healthcare applications Monitoring tumour response to therapy in real-time Reduce toxicity, prevent drug wastage Identifying disease relapse before clinically evident Pre-emptive therapy
106 Potential healthcare applications Monitoring tumour response to therapy in real-time Reduce toxicity, prevent drug wastage Identifying disease relapse before clinically evident Pre-emptive therapy Choosing intensity of adjuvant therapy based on risk stratification
107 Potential healthcare applications Monitoring tumour response to therapy in real-time Reduce toxicity, prevent drug wastage Identifying disease relapse before clinically evident Pre-emptive therapy Choosing intensity of adjuvant therapy based on risk stratification Surrogate marker of cell kill in early phase clinical trials
108 Potential healthcare applications 100 Breast cancers 100 Colorectal cancers 100 Osteosarcomas
109 Conclusions Paired-end sequencing is an effective tool for characterising structural variation in complex cancer genomes
110 Conclusions Paired-end sequencing is an effective tool for characterising structural variation in complex cancer genomes The average breast cancer has ~ 100 somatic structural variants
111 Conclusions Paired-end sequencing is an effective tool for characterising structural variation in complex cancer genomes The average breast cancer has ~ 100 somatic structural variants The average breast cancer has ~1.0 expressed in-frame fusion gene
112 Conclusions Paired-end sequencing is an effective tool for characterising structural variation in complex cancer genomes The average breast cancer has ~ 100 somatic structural variants The average breast cancer has ~1.0 expressed in-frame fusion gene Exome sequencing will unveil a multitude of novel drug targets in the next few years
113 Conclusions Paired-end sequencing is an effective tool for characterising structural variation in complex cancer genomes The average breast cancer has ~ 100 somatic structural variants The average breast cancer has ~1.0 expressed in-frame fusion gene Exome sequencing will unveil a multitude of novel drug targets in the next few years That personalised cancer care is on the horizon
114 Conclusions Paired-end sequencing is an effective tool for characterising structural variation in complex cancer genomes The average breast cancer has ~ 100 somatic structural variants The average breast cancer has ~1.0 expressed in-frame fusion gene Exome sequencing will unveil a multitude of novel drug targets in the next few years That personalised cancer care is on the horizon, and if you are wealthy enough, already here!
115
SUPPLEMENTARY INFORMATION
doi: 1.138/nature8645 Physical coverage (x haploid genomes) 11 6.4 4.9 6.9 6.7 4.4 5.9 9.1 7.6 125 Neither end mapped One end mapped Chimaeras Correct Reads (million ns) 1 75 5 25 HCC1187 HCC1395 HCC1599
The mutations that drive cancer. Paul Edwards. Department of Pathology and Cancer Research UK Cambridge Institute, University of Cambridge
The mutations that drive cancer Paul Edwards Department of Pathology and Cancer Research UK Cambridge Institute, University of Cambridge Previously on Cancer... hereditary predisposition Normal Cell Slightly
Accel-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
EXAMPLE. - 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
Whole Genome and Transcriptome Analysis of Anaplastic Meningioma. Patrick Tarpey Cancer Genome Project Wellcome Trust Sanger Institute
Whole Genome and Transcriptome Analysis of Anaplastic Meningioma Patrick Tarpey Cancer Genome Project Wellcome Trust Sanger Institute Outline Anaplastic meningioma compared to other cancers Whole genomes
BWA alignment to reference transcriptome and genome. Convert transcriptome mappings back to genome space
Whole genome sequencing Whole exome sequencing BWA alignment to reference transcriptome and genome Convert transcriptome mappings back to genome space genomes Filter on MQ, distance, Cigar string Annotate
Relationship between genomic features and distributions of RS1 and RS3 rearrangements in breast cancer genomes.
Supplementary Figure 1 Relationship between genomic features and distributions of RS1 and RS3 rearrangements in breast cancer genomes. (a,b) Values of coefficients associated with genomic features, separately
2015 EUROPEAN CANCER CONGRESS
2015 EUROPEAN CANCER CONGRESS 25-29 September 2015 Vienna, Austria SUMMARY The European Cancer Congress (ECC 2015) combined the 40th European Society for Medical Oncology (ESMO) congress with the 18th
Disclosure. 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
NGS 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
SureSelect 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
Genomic 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
FONS Nové sekvenační technologie vklinickédiagnostice?
FONS 2010 Nové sekvenační technologie vklinickédiagnostice? Sekvenování amplikonů Sequence capture Celogenomové sekvenování FONS 2010 Sekvenování amplikonů Amplicon sequencing - amplicon sequencing enables
Personalised 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
New 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
Computer Science, Biology, and Biomedical Informatics (CoSBBI) Outline. Molecular Biology of Cancer AND. Goals/Expectations. David Boone 7/1/2015
Goals/Expectations Computer Science, Biology, and Biomedical (CoSBBI) We want to excite you about the world of computer science, biology, and biomedical informatics. Experience what it is like to be a
Analysis 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
5 th July 2016 ACGS Dr Michelle Wood Laboratory Genetics, Cardiff
5 th July 2016 ACGS Dr Michelle Wood Laboratory Genetics, Cardiff National molecular screening of patients with lung cancer for a national trial of multiple novel agents. 2000 NSCLC patients/year (late
Transform 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
Cytogenetics 101: Clinical Research and Molecular Genetic Technologies
Cytogenetics 101: Clinical Research and Molecular Genetic Technologies Topics for Today s Presentation 1 Classical vs Molecular Cytogenetics 2 What acgh? 3 What is FISH? 4 What is NGS? 5 How can these
Abstract. Optimization strategy of Copy Number Variant calling using Multiplicom solutions APPLICATION NOTE. Introduction
Optimization strategy of Copy Number Variant calling using Multiplicom solutions Michael Vyverman, PhD; Laura Standaert, PhD and Wouter Bossuyt, PhD Abstract Copy number variations (CNVs) represent a significant
Genomic Instability. Kent Nastiuk, PhD Dept. Cancer Genetics Roswell Park Cancer Institute. RPN-530 Oncology for Scientist-I October 18, 2016
Genomic Instability Kent Nastiuk, PhD Dept. Cancer Genetics Roswell Park Cancer Institute RPN-530 Oncology for Scientist-I October 18, 2016 Previous lecturers supplying slides/notes/inspiration Daniel
Illumina 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
Next 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
Chromothripsis: A New Mechanism For Tumorigenesis? i Fellow s Conference Cheryl Carlson 6/10/2011
Chromothripsis: A New Mechanism For Tumorigenesis? i Fellow s Conference Cheryl Carlson 6/10/2011 Massive Genomic Rearrangement Acquired in a Single Catastrophic Event during Cancer Development Cell 144,
Clinical 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
Supplementary Figure 1. Spectrum and signatures of substitutions.
Supplementary Figure 1. Spectrum and signatures of substitutions. a. Heatmaps of trinucleotide context of substitutions. Each square represents a substitution in a specific trinucleotide context, normalised
Advance Your Genomic Research Using Targeted Resequencing with SeqCap EZ Library
Advance Your Genomic Research Using Targeted Resequencing with SeqCap EZ Library Marilou Wijdicks International Product Manager Research For Life Science Research Only. Not for Use in Diagnostic Procedures.
Multiplex target enrichment using DNA indexing for ultra-high throughput variant detection
Multiplex target enrichment using DNA indexing for ultra-high throughput variant detection Dr Elaine Kenny Neuropsychiatric Genetics Research Group Institute of Molecular Medicine Trinity College Dublin
SALSA MLPA probemix P315-B1 EGFR
SALSA MLPA probemix P315-B1 EGFR Lot B1-0215 and B1-0112. As compared to the previous A1 version (lot 0208), two mutation-specific probes for the EGFR mutations L858R and T709M as well as one additional
MET skipping mutation, EGFR
New NSCLC biomarkers in clinical research: detection of MET skipping mutation, EGFR T790M, and other important biomarkers Fernando López-Ríos Laboratorio de Dianas Terapéuticas Hospital Universitario HM
Liquid 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
Genomic structural variation
Genomic structural variation Mario Cáceres The new genomic variation DNA sequence differs across individuals much more than researchers had suspected through structural changes A huge amount of structural
Dr 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
Using the Bravo Liquid-Handling System for Next Generation Sequencing Sample Prep
Using the Bravo Liquid-Handling System for Next Generation Sequencing Sample Prep Tom Walsh, PhD Division of Medical Genetics University of Washington Next generation sequencing Sanger sequencing gold
Corporate Medical Policy
Corporate Medical Policy Molecular Panel Testing of Cancers to Identify Targeted Therapies File Name: Origination: Last CAP Review: Next CAP Review: Last Review: molecular_panel_testing_of_cancers_to_identify_targeted_therapies
Genomic analysis of childhood High grade glial (HGG) brain tumors
Genomic analysis of childhood High grade glial (HGG) brain tumors Linda D Cooley Children s Mercy, Kansas City The Children s Mercy Hospital, 2017 Genomic analysis of childhood High grade glial (HGG) brain
SALSA MLPA probemix P175-A3 Tumour Gain Lot A3-0714: As compared to the previous version A2 (lot A2-0411), nine probes have a small change in length.
SALSA MLPA probemix P175-A3 Tumour Gain Lot A3-0714: As compared to the previous version A2 (lot A2-0411), nine probes have a small change in length. This SALSA probemix is for basic research only! This
Structural Variation and Medical Genomics
Structural Variation and Medical Genomics Andrew King Department of Biomedical Informatics July 8, 2014 You already know about small scale genetic mutations Single nucleotide polymorphism (SNPs) Deletions,
Comprehensive 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
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
The feasibility of circulating tumour DNA as an alternative to biopsy for mutational characterization in Stage III melanoma patients
The feasibility of circulating tumour DNA as an alternative to biopsy for mutational characterization in Stage III melanoma patients ASSC Scientific Meeting 13 th October 2016 Prof Andrew Barbour UQ SOM
Personalised Healthcare (PHC) with Foundation Medicine (FMI) Fatma Elçin KINIKLI, FMI Turkey, Science Leader
Personalised Healthcare (PHC) with Foundation Medicine (FMI) Fatma Elçin KINIKLI, FMI Turkey, Science Leader Agenda PHC Approach Provides Better Patient Outcome FMI offers Comprehensive Genomic Profiling,
Plasma-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
Secuenciación 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.
Integration of Cancer Genome into GECCO- Genetics and Epidemiology of Colorectal Cancer Consortium
Integration of Cancer Genome into GECCO- Genetics and Epidemiology of Colorectal Cancer Consortium Ulrike Peters Fred Hutchinson Cancer Research Center University of Washington U01-CA137088-05, PI: Peters
Figure S4. 15 Mets Whole Exome. 5 Primary Tumors Cancer Panel and WES. Next Generation Sequencing
Figure S4 Next Generation Sequencing 15 Mets Whole Exome 5 Primary Tumors Cancer Panel and WES Get coverage of all variant loci for all three Mets Variant Filtering Sequence Alignments Index and align
Looking Beyond the Standard-of- Care : The Clinical Trial Option
1 Looking Beyond the Standard-of- Care : The Clinical Trial Option Terry Mamounas, M.D., M.P.H., F.A.C.S. Medical Director, Comprehensive Breast Program UF Health Cancer Center at Orlando Health Professor
Role of FISH in Hematological Cancers
Role of FISH in Hematological Cancers Thomas S.K. Wan PhD,FRCPath,FFSc(RCPA) Honorary Professor, Department of Pathology & Clinical Biochemistry, Queen Mary Hospital, University of Hong Kong. e-mail: wantsk@hku.hk
Next 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
SALSA MLPA KIT P078-B1 Breast Tumour Lot 0210, 0109
SALSA MLPA KIT P078-B1 Breast Tumour Lot 0210, 0109 This P078-B1 Breast Tumour probemix contains probes for several genes (including ERBB2, BIRC5, MYC, TOP2A, ESR1, MTDH, CCND1, CCNE1, EGFR and C11orf30)
Genomic tests to personalize therapy of metastatic breast cancers. Fabrice ANDRE Gustave Roussy Villejuif, France
Genomic tests to personalize therapy of metastatic breast cancers Fabrice ANDRE Gustave Roussy Villejuif, France Future application of genomics: Understand the biology at the individual scale Patients
Introduction to Cancer Bioinformatics and cancer biology. Anthony Gitter Cancer Bioinformatics (BMI 826/CS 838) January 20, 2015
Introduction to Cancer Bioinformatics and cancer biology Anthony Gitter Cancer Bioinformatics (BMI 826/CS 838) January 20, 2015 Why cancer bioinformatics? Devastating disease, no cure on the horizon Major
Cancer Genetics. What is Cancer? Cancer Classification. Medical Genetics. Uncontrolled growth of cells. Not all tumors are cancerous
Session8 Medical Genetics Cancer Genetics J avad Jamshidi F a s a U n i v e r s i t y o f M e d i c a l S c i e n c e s, N o v e m b e r 2 0 1 7 What is Cancer? Uncontrolled growth of cells Not all tumors
Dr C K Kwan. Associate Consultant, Queen Elizabeth Hospital, HKSAR Honorary member, Targeted Therapy Team, ICR, UK
HA Convention 2013 Dr C K Kwan MBChB, FRCR, FHKCR, FHKAM, MPM, CPI, MAppMgt(Hlth) Associate Consultant, Queen Elizabeth Hospital, HKSAR Honorary member, Targeted Therapy Team, ICR, UK To personalize cancer
MolEcular Taxonomy of BReast cancer International Consortium (METABRIC)
PERSPECTIVE 1 LARGE SCALE DATASET EXAMPLES MolEcular Taxonomy of BReast cancer International Consortium (METABRIC) BC Cancer Agency, Vancouver Samuel Aparicio, PhD FRCPath Nan and Lorraine Robertson Chair
Molecular biology of colorectal cancer
Molecular biology of colorectal cancer Phil Quirke Yorkshire Cancer Research Centenary Professor of Pathology University of Leeds, UK Rapid pace of molecular change Sequencing changes 2012 1,000 genomes
Changing demographics of smoking and its effects during therapy
Changing demographics of smoking and its effects during therapy Egbert F. Smit MD PhD. Dept. Pulmonary Diseases, Vrije Universiteit Medical Centre, Amsterdam, The Netherlands Smoking prevalence adults
Circulating 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
Select 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:
Summary... 2 TRANSLATIONAL RESEARCH Tumour gene expression used to direct clinical decision-making for patients with advanced cancers...
ESMO 2016 Congress 7-11 October, 2016 Copenhagen, Denmark Table of Contents Summary... 2 TRANSLATIONAL RESEARCH... 3 Tumour gene expression used to direct clinical decision-making for patients with advanced
AVENIO 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
Molecular classification of breast cancer implications for pathologists. Sarah E Pinder
Molecular classification of breast cancer implications for pathologists Sarah E Pinder Courtesy of CW Elston Histological types Breast Cancer Special Types 17 morphological special types 25-30% of all
XII Michelangelo Foundation Seminar
XII Michelangelo Foundation Seminar The opportunity of the neoadjuvant approach L. Gianni, Milan, I XII Michelangelo Foundation Seminar Milano, October 12, 2012 The opportunity of the neoadjuvant approach
MSI positive MSI negative
Pritchard et al. 2014 Supplementary Figure 1 MSI positive MSI negative Hypermutated Median: 673 Average: 659.2 Non-Hypermutated Median: 37.5 Average: 43.6 Supplementary Figure 1: Somatic Mutation Burden
MEDICAL 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,
Tratamiento neoadyuvante: Enfermedad residual como marcador de resistencia Carlos L. Arteaga, MD Vanderbilt-Ingram Cancer Center Vanderbilt
Tratamiento neoadyuvante: Enfermedad residual como marcador de resistencia Carlos L. Arteaga, MD Vanderbilt-Ingram Cancer Center Vanderbilt University Neoadjuvant (preoperative) therapy Surgery Systemic
Molecular Genetic Testing for the Diagnosis of Haematological Malignancies
Molecular Genetic Testing for the Diagnosis of Haematological Malignancies Dr Anthony Bench Haemto-Oncology Diagnostic Service Cambrıdge Unıversıty Hospitals NHS Foundatıon Trust Cambridge UK Molecular
Evolution of Pathology
1 Traditional pathology Molecular pathology 2 Evolution of Pathology Gross Pathology Cellular Pathology Morphologic Pathology Molecular/Predictive Pathology Antonio Benivieni (1443-1502): First autopsy
Molecular 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
Fusion genes in breast cancer
Fusion genes in breast cancer Elizabeth M. Batty Clare College, University of Cambridge A dissertation submitted to the University of Cambridge in candidature for the degree of Doctor of Philosophy November
NCCN Non-Small Cell Lung Cancer V Meeting June 15, 2018
Guideline Page and Request Illumina Inc. requesting to replace Testing should be conducted as part of broad molecular profiling with Consider NGS-based assays that include EGFR, ALK, ROS1, and BRAF as
CNV Detection and Interpretation in Genomic Data
CNV Detection and Interpretation in Genomic Data Benjamin W. Darbro, M.D., Ph.D. Assistant Professor of Pediatrics Director of the Shivanand R. Patil Cytogenetics and Molecular Laboratory Overview What
Next Generation Sequencing as a tool for breakpoint analysis in rearrangements of the globin-gene clusters
Next Generation Sequencing as a tool for breakpoint analysis in rearrangements of the globin-gene clusters XXXth International Symposium on Technical Innovations in Laboratory Hematology Honolulu, Hawaii
IntelliGENSM. 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
Figure S1. ERBB3 mrna levels are elevated in Luminal A breast cancers harboring ERBB3
Supplemental Figure Legends. Figure S1. ERBB3 mrna levels are elevated in Luminal A breast cancers harboring ERBB3 ErbB3 gene copy number gain. Supplemental Figure S1. ERBB3 mrna levels are elevated in
MEDICAL 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
MRC-Holland MLPA. Description version 18; 09 September 2015
SALSA MLPA probemix P090-A4 BRCA2 Lot A4-0715, A4-0714, A4-0314, A4-0813, A4-0712: Compared to lot A3-0710, the 88 and 96 nt control fragments have been replaced (QDX2). This product is identical to the
Supplementary Information Titles Journal: Nature Medicine
Supplementary Information Titles Journal: Nature Medicine Article Title: Corresponding Author: Supplementary Item & Number Supplementary Fig.1 Fig.2 Fig.3 Fig.4 Fig.5 Fig.6 Fig.7 Fig.8 Fig.9 Fig. Fig.11
CDH1 truncating alterations were detected in all six plasmacytoid-variant bladder tumors analyzed by whole-exome sequencing.
Supplementary Figure 1 CDH1 truncating alterations were detected in all six plasmacytoid-variant bladder tumors analyzed by whole-exome sequencing. Whole-exome sequencing of six plasmacytoid-variant bladder
Case 1. ACCME/Disclosure. Clinical History. Dr. Mulligan has nothing to disclose
Breast Evening Specialty Conference USCAP, 2016 Case 1 Anna Marie Mulligan University Health Network, Toronto University of Toronto ACCME/Disclosure Dr. Mulligan has nothing to disclose Clinical History
Introduction 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
Supplementary Figure 1. Estimation of tumour content
Supplementary Figure 1. Estimation of tumour content a, Approach used to estimate the tumour content in S13T1/T2, S6T1/T2, S3T1/T2 and S12T1/T2. Tissue and tumour areas were evaluated by two independent
Molecular Testing in Lung Cancer
Molecular Testing in Lung Cancer Pimpin Incharoen, M.D. Assistant Professor, Thoracic Pathology Department of Pathology, Ramathibodi Hospital Genetic alterations in lung cancer Source: Khono et al, Trans
Frequency(%) 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
MRC-Holland MLPA. Description version 06; 23 December 2016
SALSA MLPA probemix P417-B2 BAP1 Lot B2-1216. As compared to version B1 (lot B1-0215), two reference probes have been added and two target probes have a minor change in length. The BAP1 (BRCA1 associated
100,000 Genomes Project Update: The Cancer Programme Cancer Testing Strategy & NHS Genomic Medicine Service
100,000 Genomes Project Update: The Cancer Programme Cancer Testing Strategy & NHS Genomic Medicine Service Nirupa Murugaesu Consultant Medical Oncologist at St George s Hospital Clinical Lead for Molecular
DNA-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
The Role of Next Generation Sequencing in Solid Tumor Mutation Testing
The Role of Next Generation Sequencing in Solid Tumor Mutation Testing Allie H. Grossmann MD PhD Department of Pathology, University of Utah Division of Anatomic Pathology & Oncology, ARUP Laboratories
AVENIO 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
Breast Cancer Statistics
1 in 8 Breast Cancer Statistics Incidence Mortality Prevalence 2 Breast Cancer Incidence Breast Cancer Mortality Breast Cancer Prevalence ~$100,000 Female Breast Anatomy Breasts consist mainly of fatty
Oncology Genetics: Cytogenetics and FISH 17/09/2014
Oncology Genetics: Cytogenetics and FISH 17/09/2014 Chris Wragg Head of Oncology Genomics, BGL BGL Bristol Genetics Laboratory (BGL) CPA accredited Genetics laboratory serving a core population of 4-5million
Enabling 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
LESSON 3.2 WORKBOOK. How do normal cells become cancer cells? Workbook Lesson 3.2
For a complete list of defined terms, see the Glossary. Transformation the process by which a cell acquires characteristics of a tumor cell. LESSON 3.2 WORKBOOK How do normal cells become cancer cells?
Molecular Cell Biology. Prof. D. Karunagaran. Department of Biotechnology. Indian Institute of Technology Madras
Molecular Cell Biology Prof. D. Karunagaran Department of Biotechnology Indian Institute of Technology Madras Module 9 Molecular Basis of Cancer, Oncogenes and Tumor Suppressor Genes Lecture 2 Genes Associated
Mutation Detection and CNV Analysis for Illumina Sequencing data from HaloPlex Target Enrichment Panels using NextGENe Software for Clinical Research
Mutation Detection and CNV Analysis for Illumina Sequencing data from HaloPlex Target Enrichment Panels using NextGENe Software for Clinical Research Application Note Authors John McGuigan, Megan Manion,
"BRCAness," PARP and the Triple-Negative Phenotype
"BRCAness," PARP and the Triple-Negative Phenotype Prof Alan Ashworth, FRS Disclosures for Professor Alan Ashworth, FRS Consulting Agreements GlaxoSmithKline, Pfizer Inc Patent AstraZeneca Pharmaceuticals
Osamu Tetsu, MD, PhD Associate Professor Department of Otolaryngology-Head and Neck Surgery School of Medicine, University of California, San
Osamu Tetsu, MD, PhD Associate Professor Department of Otolaryngology-Head and Neck Surgery School of Medicine, University of California, San Francisco Lung Cancer Classification Pathological Classification
Qué 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;