Introducing Western Diagnostic s Genomic Pathology

Transcription

1 Genetic Testing

2 Introducing Western Diagnostic s Genomic Pathology As one of Australia s longest running and nationally coordinated DNA testing organisations, Western Diagnostic s Genomic Pathology perform specialised and complex DNA testing with heavy involvement from expert pathologists and scientists. Our laboratories have been providing genetic testing for over 20 years, with specialist labs across the country. We continue to lead the way in pioneering innovative genetic tests by developing and introducing the latest technologies to Australia, as well as by providing patients and doctors with access to over 3000 different genetic tests for rare and esoteric disorders, including molecular tests for more than 2000 genes through our international network. Genetic Testing Genetic tests can be performed for both non-inherited conditions (such as cancers and leukaemias) and inherited conditions (such as cystic fibrosis). They are similar to medical tests that have traditionally been provided by pathology laboratories in that they can provide answers, predict and recommend treatment options, medication efficacy, or guide reproductive options. However, they are also different in that many doctors and patients are unfamiliar with their clinical applications, power, or limitations. Some genetic tests have significant predictive power (such as the ability to confidently predict future possibility of cancer or neurological disease) and have medical implications which require specific discussion between the doctor and patient, and at times require a written consent prior to testing. Western Diagnostic s Genomic Pathology strongly emphasises a consultative service between referring doctors and our genetic specialists. We are here to provide answers to all your questions about our tests, how to access them, and their associated costs. We can help doctors and patients understand what the tests do, why they are being performed, and whether they are the most appropriate test. How to order genetic tests Many routine diagnostic genetic tests can be requested using pathology forms available through Western Diagnostic Pathology. Some tests, particularly those with complex interpretive consequences may require detailed clinical information or specialised request or consent forms. If you require further information or guidance about genetic testing requests or forms, please call , visit our website, or us on info@genomicdiagnostics.com.au Costs of genetic tests Genetic testing is often complex, requiring specialised equipment and time from highly trained medical and scientific personnel. Some genetic tests attract a full or partial rebate by Medicare and can be bulk billed at no direct cost to patients. Others require certain clinical conditions to be met in order to attract a rebate, so it is important to include appropriate clinical notes (these are denoted by an * in the list on the following pages). Many genetic tests are not funded by Medicare and attract no rebate, thus patients may incur additional costs privately. If you are unsure about the cost of a genetic test, please call , or us on info@genomicdiagnostics.com.au

3 Dr Melody Caramins B.Med, PhD, FFSc., FRCPA Western Diagnostic s Genomic Pathology is headed by Dr Melody Caramins. Dr Caramins is a nationally recognised expert in the field of genetics, holding both medical and scientific specialist qualifications. She has over 20 years of experience working in medicine and pathology, in roles including direct healthcare delivery, research, and in the provision of diagnostic services at a senior level in both public and private healthcare settings. Dr Caramins was awarded her FRCPA in 2006 as Australia s first graduate from the Genetic Pathology program, with her training undertaken in Sydney at Royal Prince Alfred Hospital and Prince of Wales Hospital. She has a longstanding interest in improving patient care by integrating research, clinical and diagnostic activities, and has published a number of journal articles highlighting this in diverse clinical settings including prenatal genetics, cancer genetics, and adult-onset genetic disorders. She continues to be an active advocate for greater access to genetic testing, and for greater inclusion of genetics in mainstream medicine through her ongoing teaching and committee activities nationally. Ms Nicole Chia MScM, FHGSA, FFSc. Associate Professor Nicole Chia is a highly experienced clinical scientist, having begun working in the field of Clinical Cytogenetics in She is a Fellow of the Royal College of Pathologists of Australasia s Faculty of Science (FFSc., RCPA) and a Fellow of the Human Genetics Society of Australasia (FHGSA). Nicole obtained her Master of Science degree in 2008 and is currently completing her PhD thesis. She has an international reputation in the field of Clinical Cytogenetics including a role as consultant to the International Standing Committee on Human Cytogenetic Nomenclature. She has been an invited speaker at numerous international and national meetings and has a number of peer reviewed scientific publications, and is an active promoter of continuing education and a senior board member of the HGSA as Chief Examiner and Chair of the Cytogenetics Board of Censors. In her role as Adjunct Associate Professor at Canberra University, Nicole continues to pursue her commitment to the education of medical scientists in the field of clinical and molecular cytogenetics, a rapidly expanding field of diagnostic pathology. Nicole is the Genetics Manager for QML pathology, Specialist Diagnostic Services and currently manages an Australia-wide diagnostic Cytogenetic and Molecular Cytogenetic Service. Dr Peter Taylor PhD, FHGSA Dr Peter Taylor is a Molecular Geneticist with solid training in general pathology prior to commencing specialisation in Peter s clinical interests include oncogenetics and neuromuscular genetics. Early in his career, Peter performed research associated with the cloning of the estrogen receptor and its regulation and role in breast cancer at the University of New South Wales. Breast cancer genetics and the study of mutations associated with breast tumours has been an area of ongoing interest throughout his career. In his PhD thesis he reported the identification the cause of a newly described neuromuscular condition, determined the clinical utility of a comprehensive screening program for X-linked muscular dystrophy, and described the correlation between gene mutation location and cognitive defects in Duchenne muscular dystrophy. He has several highly read peer-reviewed papers and has contributed to numerous conference papers. He is a Fellow of the Human Genetics Society of Australasia (FHGSA) and is the immediate past Chair for the Molecular Genetics Society of Australasia (MGSA), acting as an examiner for the annual examinations. He is the Scientific Director for Molecular Testing at Western Diagnostic s Genomic Pathology, Specialist Diagnostic Services, and currently manages human and animal molecular genetic testing. Dr Simon Cliffe PhD, FHGSA Dr Serguei Kovalenko PhD Dr Simon Cliffe has worked in the field of medical genetics in diagnostic and research capacities for more than 11 years. He was awarded his PhD in 2012, in a project leading to the discovery of the genetic basis of two autosomal recessive genetic disorders, including publications in leading journals such as Nature Genetics and Human Molecular Genetics. His diagnostic experience includes senior roles in academic hospital settings, and he was awarded his FHGSA in He is a divisional head with reporting responsibility located in Victoria, and has a particular interest in translating novel research findings in inherited and somatic genetics into deliverable clinical tests for patients and doctors, with a focus on next-generation sequencing technologies. Dr Serguei Kovalenko obtained his PhD in Molecular Cytogenetics in 1992 investigating the pharmacogenomics of anthracycline antiobiotics utilised in the treatment of cancer. Prior to joining Western Diagnostic s Genomic Pathology, Serguei was Head of Medical Diagnostics at Genetic Technologies Corporation, and also served as Molecular Pathology Diagnostic Laboratory Manager at Peter MacCallum Cancer Centre in Melbourne. He is the author of more than 30 refereed articles, including prestigious journals such as Nature and Nature Genetics. Dr Kovalenko is a curator of the MutaBase mutation database and an active member of the HGSA, EviQ, KConFab and HUGO professional societies. He is a divisional manager with reporting responsibility at our Melbourne site, with professional interests including the molecular basis of hereditary and somatic genetic disorders, molecular diagnostic testing and bioinformatic solutions for molecular diagnostics.

4 Our Team Test Name Inherited Haematological Disorders Brief description of disease, indication and method Medicare Eligibility Alpha Thalassaemia Screen Diagnosis of alpha thalassaemia carriers by detection of selected causative variants Factor V Leiden mutation detection Diagnosis of hereditary thrombophilia predisposition by detection of causative variant or testing of a first degree relative of a person with a proven abnormal genotype * Each member of our senior team has worked in a nationally recognised leadership role as academics, researchers, and diagnosticians. They have also participated in professional societies at the highest levels through their contributions to the development of testing guidelines and standards, or as examiners and speakers. We bring our experience to you, and we are available for advice and consultation on technical or clinical matters. Western Diagnostic s Genomic Pathology is not just about providing a result. We are here to support your management decisions by providing guidance about the best choice of tests, helping in the interpretation of results, and by ensuring that testing provided meets the highest quality and accreditation standards. Prothrombin gene mutation detection Hereditary haemochromatosis Haematological Oncology WHOLE CHROMOSOME TESTS FISH TESTS (FLUORESCENCE IN SITU HYBRIDISATION), USING DNA PROBES TO DETECT SPECIFIC CHROMOSOME ABNORMALITIES WITHIN BLOOD AND BONE MARROW TUMOUR CELLS. THE INDIVIDUAL FISH PROBES USED WILL VARY BY THE SPECIFIC TYPE OF CANCER BEING EVALUATED. LEUKAEMIAS ARE LISTED ALPHABETICALLY (also known as karyotype) Chromosome analysis by microarray (also known as molecular karyotype) Diagnosis of hereditary thrombophilia predisposition by detection of causative variant or testing of a first degree relative of a person with a proven abnormal genotype Diagnosis of hereditary haemochromatosis predisposition by detection of causative variants or testing of a first degree relative of a person with a proven abnormal genotype Microscopic analysis of all chromosomes to examine structure, rearrangements, and number; used for the invesitagion of haematological malignancies Submicroscopic analysis of all chromosomes to determine genomic losses and amplifications; used for the investiagion of haematological malignancies AML FISH AML/ETO t(8;21)(q22;q22) FISH in acute myeloid leukaemia (AML) RUNX1/RUNX1T1 t(8;21) FISH Acute myeloid leukaemia (AML), t(8;21)(q22;q22) FISH (AML/ETO) AML FISH panel Acute myeloid leukaemia (AML), panel (multiple) FISH ALL FISH panel Acute lymphocytic leukaemia (ALL), panel (multiple) FISH PML/RARA t(15;17) FISH Acute promelocytic leukaemia (APML), FISH for (15;17)(q22;q21.1) IGH 14q32 FISH B-cell disorders MLL 11q23 FISH B-cell leukaemias 1;19 rearrangements FISH B-cell lymphocytic leukaemia/lymphoma Lymphoma panel FISH B-cell panel (multiple) FISH MYC 8q24 FISH B-cell lymphomas BIRC3/MALT t(11:18) FISH B-cell lymphomas IGK 2p11.2 FISH B-cell lymphomas * * IGL 2p11.2 FISH B-cell lymphomas IGH/MYC/CEP8 t(8;14) FISH Burkitt's lymphoma/ -like leukaemia IGH/BCL2 t(14;18) FISH Follicular lymphoma IGH/CCND1-XT t(11;14) FISH Mantle cell lymphoma/cll CLL FISH panel Chronic lymphocytic leukaemia (CLL) panel (multiple) FISH ATM 11q23 FISH Chronic lymphocytic leukaemia (CLL), FISH for ATM deletions (11q23) Trisomy 12 FISH Chronic lymphocytic leukaemia (CLL) MYB 6q23 FISH Chronic lymphocytic leukaemia (CLL) TP53 FISH Chronic lymphocytic leukaemia (CLL), FISH for TP53 17p13 deletions 13q FISH Chronic lymphocytic leukaemia (CLL), FISH for 13q14.3 deletions PDGFRB 5q32 FISH Chronic myelomonocytic leukaemia BCR / ABL (FISH or molecular testing, as requested) Chronic myeloid leukaemia (CML) FISH for t(9;22)(q34;q11.2), or quantitative testing via RT PCR. Also used in ALL. Trisomy/monosomy 7 FISH Leukaemias, various, including treatment-related Multiple myeloma FISH panel Multiple myeloma (MM) panel (multiple) FISH

5 Test Name Brief description of disease, indication and method Medicare Eligibility FISH TESTS (FLUORESCENCE IN SITU HYBRIDISATION), USING DNA PROBES TO DETECT SPECIFIC CHROMOSOME ABNORMALITIES WITHIN BLOOD AND BONE MARROW TUMOUR CELLS. THE INDIVIDUAL FISH PROBES USED WILL VARY BY THE SPECIFIC TYPE OF CANCER BEING EVALUATED. LEUKAEMIAS ARE LISTED ALPHABETICALLY 1pq (CKS1B/CDKN2) FISH Multiple myeloma (MM), FISH for amplification/deletion 1q21/1p32.3 IGH/FGFR3 t(4;14) FISH Multiple myeloma (MM), FISH for t(4;14)(p16.3;q32) IGH/MAF t(14;16) FISH Multiple myeloma (MM) IGH/MAFB t(14;20) FISH Multiple myeloma (MM) Myelodysplastic panel FISH Myelodysplastic syndrome, multiple FISH panel 1pq 1p36/1q25 FISH Myeloid and lymphoid leukaemias Trisomy 9 FISH Myeloid and lymphoid leukaemias FIP1L1/PDGFRA: CHIC2- deletion 4q12 FISH Myeloid and lymphoid neoplasms EVI1 3q26.2 FISH Myeloid leukaemias 5q- syndrome Myeloid neoplasms, 5q31.2 FISH for deletion 7q deletion 7q22/7q31 FISH Myeloid neoplasms FGFR1 8p12 FISH Myeloproliferative disorders 20q deletion FISH Myeloproliferative disorders/myeloid neoplasms BCL6 3q26 FISH Non-hodgkin lymphomas IGH/MALT1 t(14;18)(q32;q21) FISH Non-hodgkin lymphomas PAX 5 9p12 FISH Non-hodgkin lymphomas TCL1 14q32.13 FISH T-cell leukaemias MOLECULAR TESTS CALR gene test Molecular testing for CALR exon 9 variants, myeloproliferative disorders/myeloid neoplasms FLT3 gene test Acute myeloid leukaemia (AML), molecular testing for specific variants in FLT3 gene JAK2 gene test Molecular testing for specific variants in JAK2, myeloproliferative disorders/myeloid neoplasms * Lymphocyte gene rearrangement studies Lymphocyte gene rearrangement studies B-Cell lymphoproliferative disorders, detection of B-Cell immunoglobulin gene rearrangements for the detection of clonality T-cell lymphoproliferative disorders, T-Cell receptor gene rearrangements for the detection of clonality MPL gene test Molecular testing for specific variants, myeloproliferative disorders/myeloid neoplasms * NPM1 gene test Acute myeloid leukaemia (AML), molecular testing for specified variants of nucleophosmin gene (NPM1) Solid Tumour Oncology Pharmacogenetics (see also Molecular Cytogenetics section) ALK gene 2p23 FISH Testing for ALK gene (2p23) rearrangements by FISH in non small cell lung cancer (NSCLC) * BRAF gene test Testing for actionable variants in BRAF gene in melanoma * Cancer Origin Test For investigation of cancers of unknown primary EGFR gene test Testing for actionable variants in EGFR gene in non small cell lung cancer (NSCLC) * RAS gene test Testing for actionable variants in KRAS and NRAS genes in colorectal cancer * Tumour molecular profiling by massively parallel sequencing (Ideally suited for molecular profiling of lung, melanoma, colon, gastric, and ovarian malignancies) AKT1, ALK, APC, BRAF, CDH1, CTNNB1, EGFR, ERBB2, FBXW7, FGFR2, FOXL2, GNAQ, GNAS, KIT, KRAS, MAP2K1, MET, MSH6, NRAS, PDGFRA, PIK3CA, PTEN, SMAD4, SRC, STK11, TP53, selected exons. Molecular testing for specific variants. All exons of selected genes (e.g. KRAS and NRAS), some genes only include specified actionable variants. Eligible in clinical circumstances which meet MBS criteria for EGFR or RAS testing

6 Test Name Other Pharmacogenetics TPMT genotyping Inherited Immunological Brief description of disease, indication and method Testing for specific variants in the TPMT gene to predict dosage of azathioprine and 6-mercaptopurine Medicare Eligibility Ankylosing Spondilitis HLA-B27 genotyping in association with CRP testing Coeliac disease Genotyping for variants of HLA DQ2 and DQ8 in association with other tests Respiratory, Fertility and Development Alpha-1 Antitrypsin gene test SERPINA1 molecular genetic testing (karyotyping) Used in the investigation of genetic causes of male and female infertility Cystic fibrosis genetic testing Confirmation of suspected cystic fibrosis, or for carrier testing Cystic fibrosis genetic testing Used in the investigation of genetic causes of male infertility, or for preconception carrier testing Fragile X genetic testing Used in the investigation of premature ovarian insufficiency * Y Chromosome microdeletion analysis Used in the investigation of male infertility (AZF, DAZ) Non-invasive prenatal testing (NIPT) Inherited Cancer Genetic Testing INHERITED BREAST/ OVARIAN CANCER Ashkenazi BRCA1/2 founder mutation test BRCA1 and BRCA2 comprehensive test (both genes) BRCA1 or BRCA2 comprehensive test (single gene) BRCA1 or BRCA2 predictive Test Used to detect common foetal genetic chromosome abnormalities. This is a rapidly changing area of testing; please contact the laboratory for details Detection of ethnic-specific hereditary breast/ovarian cancer susceptibility variants Inherited breast/ovarian cancer, sequencing and copy number analysis of BRCA1 and BRCA2 Sequencing and copy number analysis of single gene (BRCA1 or BRCA2) Detection of a single family-specific DNA variant in inherited breast/ovarian cancer # # # # INHERITED BOWEL/ ENDOMETRIAL CANCER Lynch Syndrome, gene panel Comprehensive sequencing and copy number of multiple genes (MLH1, MSH2, MSH6, PMS2, MYH and EPCAM) in hereditary bowel/endometrial cancer (Lynch Syndrome) # Lynch Syndrome, single gene Single gene comprehensive test, sequencing and copy number analysis, in hereditary bowel/endometrial cancer (Lynch Syndrome) # Lynch Syndrome, predictive test Detection of a family-specific DNA variant in hereditary bowel/endometrial cancer (Lynch Syndrome) # Cardiovascular APOE gene variant detection Detection of hyperlipoproteinaemia and cardiovascular risk MTHFR gene variant detection Homocysteine and folate metabolism in conjunction with other tests *Only if fulfilling clinical criteria for inherited thrombophilia risk testing and performed with conjunction with prothrombin and factor V Leiden mutation detection * Molecular Cytogenetics (inherited disorders and solid tumours) WHOLE CHROMOSOME TESTS Chromosome analysis by microarray (molecular karyotyping) Chromosome analysis by microarray (molecular karyotyping) - prenatal and products of conception Molecular (submicroscopic) analysis of chromosome imbalances, used in the investigation of autism, developmental delay, or multiple congenital abnormalities Used in the investigation of genetic causes for high risk pregnancies with foetal anomalies, or after foetal demise *

7 Test Name Brief description of disease, indication and method Medicare Eligibility FISH TESTS 1p36 microdeletion syndrome FISH Specified microdeletion diagnosis using FISH probes for genes at 1p36 * Cytogenetics 22q microdeletion syndrome FISH Diagnosis of 22q Microdeletion Syndrome using FISH probes at 22q13 * Alveolar Rhabdomyosarcoma FISH FKHR 13q14 FISH Angelman FISH Diagnosis of Angelman Syndrome using FISH probes at 15q11.2-q14 * Aneuploidy - detection of common trisomies prenatally (13,18,21) Diagnosis of trisomies 13, 18, and 21 by FISH or by QF-PCR. Down Syndrome, Edward Syndrome, Patau Syndrome Cri du Chat FISH Diagnosis of Cri du Chat Syndrome using FISH probes at EGR1 * Di George/VCFS FISH Diagnosis of Di George/VCFS Syndrome using FISH probes at 22q11.2 * Ewings Sarcoma FISH EWSR1 22q12 FISH Glioma FISH GLI 12q13 FISH Liposarcoma FISH CHOP 12q13 FISH Liposarcoma FISH FUS 16p11 FISH Miller-Dieker FISH Diagnosis of Miller-Dieker Syndrome using FISH probes at LIS1 * MDM2 amplification 12q14.3 FISH Various Neoplasms Prader Willi FISH Diagnosis of Prader Willi Syndrome using FISH probes at 15q11.2-q13 * Sex determination Diagnosis of sex chromosome imbalances for chromosomes X and Y by FISH or QF-PCR Smith-Magenis FISH Diagnosis of Smith-Magenis Syndrome using FISH probes at RAR1 * Sotos FISH Diagnosis of Sotos Syndrome using FISH probes at NSD1 * Synovial sarcoma FISH SYT 18q11.2 FISH Williams-Beuren FISH Diagnosis of Williams-Beuren Syndrome using FISH probes at ELN * Wolf-Hirschorn FISH Diagnosis of Wolf-Hirschorn Syndrome using FISH probes for genes at 4p * X inactivation FISH Diagnosis of X Inactivation Syndrome using FISH probes at XIST * Xp Yp deletions FISH Diagnosis of Xp Yp Deletions using FISH probes at SHOX * Yp rearrangements FISH Diagnosis of Yp rearrangements using SRY probe * (karyotyping) (karyotyping)- prenatal (karyotyping)- products of conception Other Molecular Genetic Testing Dravet Syndrome, inherited seizures, inherited epilepsy Dravet Syndrome, inherited seizures, inherited epilepsy Fragile X testing Non Medical Genetic Testing Microscopic analysis of chromosome structure and number, used for multiple indications Used in the investigation of genetic causes of foetal abnormalities and for the investigation of high risk pregnancies Used in the investigation of genetic causes of foetal abnormalities and foetal demise SCN1A Comprehensive Test SCN1A Mutation Segregation Analysis Diagnosis and carrier testing for Fragile X related disorders, including Fragile X tremor and ataxia, premature ovarian insufficiency, and developmental delay Gilbert Syndrome Diagnosis of benign hyperbilirubinaemia by detection of specific variants in UGT1A1 SCA 8 genetic testing Diagnosis of autosomal dominant ataxia caused by expansion mutations of ATXN8 Sendaway tests via our international network (over 3000 genetic tests) Relationship testing Tests for rare genetic conditions via an accredited laboratory network Provision of genetic evidence regarding biological relationship for legal, immigration or peace of mind purposes. See website for further details *

8 For clinical enquiries, please contact: Pathologist in Charge, Dr Melody Caramins Ph: