Associate Professor Amanda Spurdle has more than 20 years of experience in the field of molecular genetic epidemiology of hormone-related cancers, including breast, ovarian, prostate, endometrial and colon cancer. She have been an active member of the Breast Cancer Association Consortium (BCAC) and an equivalent consortium for prostate cancer research PRACTICAL. Amanda initiated the international Endometrial Cancer Association Consortium (ECAC) to identify low-risk endometrial cancer genes, published the first study to identify an endometrial cancer locus using a genome-wide association study approach, and have expanded this work to include functional analysis.
She is also directly involved in research aiming to use advanced molecular methods to improve the identification of individuals with hereditary colorectal, endometrial cancer, or breast cancer. She developed the first model to classify variants in the colorectal-endometrial cancer mismatch repair genes, and led the effort by the InSiGHT consortium (International Society for Gastrointestinal Hereditary Tumours) to standardize the clinical interpretation of mismatch repair genes variants in the InSiGHT database. This group has been recognized by the ClinGen consortium as an expert panel for classification of MMR gene variants in the ClinVar database. Amanda co-founded and now leads the ENIGMA international consortium (Evidence-based Network for Interpretation of Germline Mutant Alleles), which aims to develop statistical and laboratory methods to evaluate variants of uncertain clinical significance in known and suspected breast cancer predisposition genes. In addition, she leads the ENIGMA sub-committee for classification of BRCA1/2 variants, recognized by the ClinGen consortium as an expert panel for BRCA1/2 variant classification for ClinVar.
Amanda co-ordinates the variant interpretation activities of the BRCA Challenge project initiated by the Global alliance for Genomics & Health, which disseminates information relevant to BRCA1/2 variant curation via the public portal http://brcaexchange.org/. The large majority of my >300 publications focus on the relationship between genetic variation and cancer risk, covering epidemiological, biological and molecular studies.
Current QIMR Berghofer appointment
- 2014 – present: NHMRC Senior Research Fellow Level B
- 2003 – present: Head, Molecular Cancer Epidemiology Laboratory, QIMR Berghofer MRI
Other current appointments
- 2011 – present: Adjunct Associate Professor, promoted to Adjunct Professor 2017, Cell & Molecular Biosciences Discipline, Faculty of Science & Technology, Queensland University of Technology
- 2001 – present: Conjoint Lecturer, promoted to Adjunct Professor 2011, School of Medicine, Faculty of Health Sciences, University of Queensland
- 2009 – 2013: NHMRC Senior Research Fellow Level A
- 2008: QIMR Senior Research Fellow
- 2006 – 2011: Honorary Fellow, School of Public Health, QUT
- 2003 – 2007: NHMRC RD Wright Fellow
- 2000 – 2002: Senior Research Officer, Cancer Genetics Laboratory, Cancer and Cell Biology Division, QIMR
- 1997 – 1999: Research Officer, Cancer Genetics Laboratory, Cancer and Cell Biology Division, QIMR
- 1994 – 1997: Research Officer, School of Genetics and Human Variation, La Trobe University
- 1987 – 1994: Medical Scientist, Department of Human Genetics, South African Institute of Medical Research
Current Area of Research
I have an active program in the field of unclassified variants identified in high-moderate risk cancer genes, with a focus on breast/ovarian and endometrial/colorectal cancer predisposition syndromes. I use bioinformatics, laboratory and statistical methods to assess the functional and clinical significance of these variants. My research includes development of clinically useful tools for the classification of sequence variants mapping to regulatory regions of BRCA1/2 and non-BRCA1/2 breast cancer susceptibility genes. I am also conducting large-scale association studies of >11M genetic markers to identify additional novel risk variants and genes important in endometrial cancer aetiology, and sequencing studies of endometrial cancer patients with strong family history of cancer to identify novel cancer syndrome genes.
I initiated an international collaborative effort to demonstrate, for the first time, that a BRCA1 variant demonstrating intermediate activity in functional assays was associated with an intermediate level of risk. This innovative finding spurred on new angles of research from an analytical and clinical perspective, and led to the formal establishment of the ENIGMA consortium. Multiple other research studies have demonstrated need to standardise laboratory and assay interpretation protocols for clinical application. I was the first to show clinical classification of variants in the familial colorectal-endometrial cancer mismatch repair (MMR) genes is assisted by a comprehensive approach which includes in vitro, tumor pathology, clinical, and evolutionary conservation data, and first to develop a robust multifactorial likelihood model for classification MMR gene variants. I co-led a landmark effort to apply a 5-tiered scheme for standardized classification to 2,360 unique mismatch repair gene variants in the InSiGHT locus-specific database. Findings highlighted the need for standardized and normalised classification using expert curation for accurate and reliable variant classification, and showed the value of microattribution as a scheme to encourage data submission to public databases.
I set up a large Australian national endometrial cancer case-control-family study, with internationally unique features of design and bioresource collection, aimed in part to provide data to inform public health policy on endometrial cancer risk and assist development of a clinical guide for familial endometrial cancer risk. A major outcome of my research is the description of a cost-effective and efficient scheme to identify endometrial cancer patients for germline mutation testing of mismatch repair (MMR) genes, as a means to encourage family cascade testing and screening and prevention of cancers in high-risk individuals. Building on my own endometrial cancer association studies, I initiated the Endometrial Cancer Association Consortium, which has already brought together 13 groups for combined approaches to studying genetic factors of importance to endometrial cancer risk, and also to use genetic markers to confirm causal relationships between epidemiological factors/exposures and endometrial cancer risk using Mendelian Randomization approaches. I published the first genome-wide association study of endometrial cancer, identifying the HNF1B locus as a risk locus for endometrial cancer. I have since extended this research to triple the number of identified endometrial cancer risk loci identified by GWAS.
- 2016: Member, ClinGen Expert panel for TP53 variant classification
- 2016: Member, ClinGen Expert panel for CDH1 variant classification
- 2015: Steering committee member and head of Variant Interpretation Group, GA4GH initiated BRCA Challenge project
- 2013: Head, ClinGen-approved ENIGMA Expert panel for BRCA1/2 variant classification
- 2009: Co-founder & current Executive Committee chair, ENIGMA consortium for evaluating breast cancer gene variants
- 2009: Member, ClinGen-approved Expert panel for MMR gene variant classification, the Intl Society for Gastointestinal Hereditary Tumours Variant Interpretation Committee
- 2003: Chair, Kathleen Cuningham Foundation Consortium for research into Familial Breast cancer (KConFaB) Mutation Review Committee and member, Executive Committee
- 1984: B Sc (Biological Sciences), University of Witwatersrand, South Africa
- 1985: B Sc, Hons (Botany), University of Witwatersrand, South Africa
- 1986: M Sc (Biotechnology), University of Witwatersrand, South Africa
- 1992: PhD (Human Population Genetics), University of Witwatersrand, South Africa