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https://repository.monashhealth.org/monashhealthjspui/handle/1/49855| Title: | Ovarian cancer pathology characteristics as predictors of variant pathogenicity in BRCA1 and BRCA2. | Authors: | O'Mahony D.G.;Ramus S.J.;Southey M.C.;Meagher N.S.;Hadjisavvas A.;John E.M.;Hamann U.;Imyanitov E.N.;Andrulis I.L.;Sharma P.;Daly M.B.;Hake C.R.;Weitzel J.N.;Jakubowska A.;Godwin A.K.;Arason A.;Bane A.;Simard J.;Soucy P.;Caligo M.A.;Mai P.L.;Claes K.B.M.;Teixeira M.R.;Chung W.K.;Lazaro C.;Hulick P.J.;Toland A.E.;Pedersen I.S.;Mourits M.J.E.;Neuhausen S.L.;Vega A.;Nevanlinna H.;Dhawan M.;Zampiga V.;Danesi R.;Varesco L.;Gismondi V.;Vellone V.G.;James P.A.;Janavicius R.;Nikitina-Zake L.;Nielsen F.C.;Pejovic T.;Borg A.;Rantala J.;Offit K.;Montagna M.;Nathanson K.L.;Domchek S.M.;Osorio A.;Garcia M.J.;Karlan B.Y.;Lesueur F.;Bowtell D.;De Fazio A.;McGuffog L.;Leslie G.;Parsons M.T.;Dork T.;Speith L.-M.;da Costa A.A.B.A.;Radice P.;Peterlongo P.;Papi L.;Engel C.;Hahnen E.;Schmutzler R.K.;Wappenschmidt B.;Easton D.F.;Tischkowitz M.;Singer C.F.;Tan Y.Y.;Whittemore A.S.;Sieh W.;Brenton J.D.;Yannoukakos D.;Fostira F.;Konstantopoulou I.;Soukupova J.;Vocka M.;Chenevix-Trench G.;Pharoah P.D.P.;Antoniou A.C.;Goldgar D.E.;Spurdle A.B.;Michailidou K.;de la Hoya M.;van Overeem Hansen T.;dos Santos E.S. | Monash Health Department(s): | Monash University - School of Clinical Sciences at Monash Health | Institution: | (O'Mahony, Michailidou) Biostatistics Unit, The Cyprus Institute of Neurology and Genetics, Nicosia 2371, Cyprus (O'Mahony, Hadjisavvas) Department of Cancer Genetics, Therapeutics and Ultrastructural Pathology, The Cyprus Institute of Neurology and Genetics, Nicosia 2371, Cyprus (Ramus, Meagher) School of Clinical Medicine, University of New South Wales Medicine and Health, University of New South Wales Sydney, Sydney, NSW 2052, Australia (Ramus, Meagher) Adult Cancer Program, Lowy Cancer Research Centre, University of New South Wales Sydney, Sydney, NSW 2052, Australia (Southey) Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC 3168, Australia (Southey) Department of Clinical Pathology, The University of Melbourne, Melbourne, VIC 3010, Australia (Southey) Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, VIC 3004, Australia (Meagher, De Fazio, De Fazio) The Daffodil Centre, The University of Sydney, a joint venture with Cancer Council NSW, Sydney, NSW, Australia (John, Whittemore) Department of Epidemiology and Population Health, Stanford University School of Medicine, Stanford, CA 94305, United States (John) Department of Medicine, Division of Oncology, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94304, United States (Hamann) Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany (Hahnen, Schmutzler, Wappenschmidt) Center for Familial Breast and Ovarian Cancer, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne 50937, Germany (Hahnen, Schmutzler, Wappenschmidt) Center for Integrated Oncology (CIO), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne 50937, Germany (Schmutzler) Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne 50931, Germany (Easton, Pharoah) Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge CB1 8RN, United Kingdom (Tischkowitz) Program in Cancer Genetics, Departments of Human Genetics and Oncology, McGill University, Montreal, QC H4A 3J1, Canada (Tischkowitz) Department of Medical Genetics, National Institute for Health Research Cambridge Biomedical Research Centre, University of Cambridge, Cambridge CB2 0QQ, United Kingdom (Singer, Tan) Department of OB/GYN and Comprehensive Cancer Center, Medical University of Vienna, Vienna 1090, Austria (Whittemore) Department of Biomedical Data Science, Stanford University School of Medicine, Stanford, CA 94305, United States (Sieh) Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States (Sieh) Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States (Brenton) Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, United Kingdom (Yannoukakos, Fostira, Konstantopoulou) Molecular Diagnostics Laboratory, INRASTES, National Centre for Scientific Research 'Demokritos', Athens 15310, Greece (Soukupova) Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague 12000, Czechia (Vocka) Department of Oncology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague 12000, Czechia (Chenevix-Trench) Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia (Goldgar) Department of Dermatology, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT 84112, United States (Mourits) Department of Obstetrics and Gynecology, University Medical Center Groningen, University Groningen, Groningen 9713 GZ, Netherlands (Mourits) The Hereditary Breast and Ovarian Cancer Research Group Netherlands (HEBON), Coordinating Center: The Netherlands Cancer Institute, Amsterdam 1066 CX, Netherlands (Lesueur) Genetic Epidemiology of Cancer team, Inserm U900, Paris 75005, France (Lesueur) Institut Curie, Paris 75005, France (Lesueur) Mines ParisTech, Fontainebleau 77305, France (Imyanitov) N.N. Petrov Institute of Oncology, St. Petersburg 197758, Russian Federation (Andrulis) Fred A. Litwin Center for Cancer Genetics, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, ON M5G 1x5, Canada (Andrulis) Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada (Sharma) Department of Internal Medicine, Division of Medical Oncology, University of Kansas Medical Center, Westwood, KS 66205, United States (Daly) Department of Clinical Genetics, Fox Chase Cancer Center, Philadelphia, PA 19111, United States (Hake) Waukesha Memorial Hospital-Pro Health Care, Waukesha, WI 53188, United States (Weitzel) The University of Kansas Cancer Center, Kansas City, MO 66160, United States (Jakubowska) Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin 171-252, Poland (Jakubowska) Independent Laboratory of Molecular Biology and Genetic Diagnostics, Pomeranian Medical University, Szczecin 171-252, Poland (Godwin) Department of Pathology and Laboratory Medicine, The University of Kansas Medical Center, Kansas City, KS 66160, United States (Arason) Department of Pathology, Landspitali University Hospital, 101, Reykjavik, Iceland (Arason) BMC (Biomedical Centre), Faculty of Medicine, University of Iceland, Reykjavik 101, Iceland (Bane) Department of Pathology & Molecular Medicine, Juravinski Hospital and Cancer Centre, McMaster University, Hamilton, ON L8V 1C3, Canada (Simard, Soucy) Genomics Center, Centre Hospitalier Universitaire de Quebec - Universite Laval Research Center, Quebec City, QC G1V 4G2, Canada (Caligo) SOD Genetica Molecolare, University Hospital, Pisa 56126, Italy (Mai) Magee-Womens Hospital, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, United States (Claes) Centre for Medical Genetics, Ghent University, Gent 9000, Belgium (Teixeira) Department of Laboratory Genetics, Portuguese Oncology Institute of Porto (IPO Porto)/Comprehensive Cancer Center, Porto 4200-072, Portugal (Teixeira) School of Medicine and Biomedical Sciences Institute (ICBAS), University of Porto, Porto 4050-013, Portugal (Chung) Departments of Pediatrics and Medicine, Columbia University, New York, NY 10032, United States (Lazaro) Hereditary Cancer Program, ONCOBELL-IDIBELL-IGTP, Catalan Institute of Oncology, CIBERONC, Barcelona 08908, Spain (Hulick) Center for Medical Genetics, NorthShore University HealthSystem, Evanston, IL 60201, United States (Hulick) The University of Chicago Pritzker School of Medicine, Chicago, IL 60637, United States (Toland) Department of Cancer Biology and Genetics, The Ohio State University, Columbus, OH 43210, United States (Pedersen) Molecular Diagnostics, Aalborg University Hospital, Aalborg 9000, Denmark (Pedersen) Clinical Cancer Research Center, Aalborg University Hospital, Aalborg 9000, Denmark (Pedersen) Department of Clinical Medicine, Aalborg University, Aalborg 9000, Denmark (Neuhausen) Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, CA 91010, United States (Vega) Centro de Investigacion en Red de Enfermedades Raras (CIBERER), Madrid 28029, Spain (Vega) Fundacion Publica Galega de Medicina Xenomica, Santiago de Compostela 15706, Spain (Vega) Instituto de Investigacion Sanitaria de Santiago de Compostela (IDIS), Complejo Hospitalario Universitario de Santiago, SERGAS, Santiago de Compostela 15706, Spain (de la Hoya, de la Hoya) Molecular Oncology Laboratory, CIBERONC, Hospital Clinico San Carlos, IdISSC (Instituto de Investigacion Sanitaria del Hospital Clinico San Carlos), Madrid 28040, Spain (Nevanlinna) Department of Obstetrics and Gynecology, Helsinki University Hospital, University of Helsinki, Helsinki 00290, Finland (Dhawan) Cancer Genetics and Prevention Program, University of California San Francisco, San Francisco, CA 94143-1714, United States (Zampiga) Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy (Danesi) Romagna Cancer Registry, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola 47014, Italy (Varesco, Gismondi) Unit of Hereditary Cancer, IRCCS Ospedale Policlinico San Martino, Genoa 16132, Italy (Vellone) Unit of Pathology, IRCCS Ospedale Policlinico San Martino, Genoa 16132, Italy (James) Department of Gynecology and Obstetrics, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto 14049-900, Brazil (Janavicius) Faculty of Medicine, Institute of Biomedical Sciences, Department of Human and Medical Genetics, Vilnius University, Vilnius LT-03101, Lithuania (Janavicius) State Research Institute Centre for Innovative Medicine, Vilnius 8410, Lithuania (Nikitina-Zake) Latvian Biomedical Research and Study Centre, Riga LV-1067, Latvia (Nielsen) Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital, Copenhagen DK-2100, Denmark (van Overeem Hansen, van Overeem Hansen) Department of Clinical Genetics, Rigshospitalet, Copenhagen University Hospital, Copenhagen DK-2100, Denmark (van Overeem Hansen, van Overeem Hansen) Department of Clinical Medicine, Faculty of Health and Medical Sciences, , University of Copenhagen, Copenhagen 2200, Denmark (Pejovic) Department of Obstetrics and Gynecology, Oregon Health & Science University, Portland, OR 97239, United States (Pejovic) Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, United States (Borg) Department of Oncology, Lund University and Skane University Hospital, Lund 222 41, Sweden (Rantala) Clinical Genetics, Karolinska Institutet, Stockholm 171 76, Sweden (Offit) Clinical Genetics Research Lab, Department of Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, United States (Offit) Clinical Genetics Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, United States (Montagna) Immunology and Molecular Oncology Unit, Veneto Institute of Oncology IOV - IRCCS, Padua 35128, Italy (Nathanson, Domchek) Basser Center for BRCA, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA 19066, United States (Osorio) Human Genetics Group, Spanish National Cancer Research Centre (CNIO), Madrid 28029, Spain (Osorio) Centre for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Madrid 28029, Spain (Osorio) Genetics Service, Fundacion Jimenez Diaz, Madrid 28040, Spain (Garcia) Computational Oncology Group, Structural Biology Programme, Spanish National Cancer Research Centre (CNIO), Madrid 28029, Spain (Karlan) David Geffen School of Medicine, Department of Obstetrics and Gynecology, University of California at Los Angeles, Los Angeles, CA 90095, United States (De Fazio, De Fazio) Centre for Cancer Research, The Westmead Institute for Medical Research, Sydney, Australia (De Fazio, De Fazio) Department of Gynaecological Oncology, Westmead Hospital, Sydney, NSW 2145, Australia (De Fazio, De Fazio) The University of Sydney, Sydney, NSW 2145, Australia (Bowtell) Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia (Bowtell) Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, VIC 3000, Australia (McGuffog, Leslie, Easton, Pharoah, Antoniou, Michailidou) Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, United Kingdom (Parsons, Spurdle) Population Health Program, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia (Dork, Speith) Gynaecology Research Unit, Hannover Medical School, Hannover 30625, Germany (dos Santos, dos Santos) Service de Genetique, Institut Curie, Paris 75005, France (dos Santos, dos Santos) Oncology Center, Hospital Sirio-Libanes, Sao Paulo 01308-050, Brazil (dos Santos, da Costa, dos Santos) Department of Clinical Oncology, A.C.Camargo Cancer Center, Sao Paulo 1509900, Brazil (da Costa) Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA 2215, United States (Radice) Unit of Preventive Medicine: Molecular Bases of Genetic Risk, Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Milan 20133, Italy (Peterlongo) Genome Diagnostics Program, IFOM ETS - the AIRC Institute of Molecular Oncology, Milan 20139, Italy (Papi) Department of Experimental and Clinical Biomedical Sciences 'Mario Serio', Medical Genetics Unit, University of Florence, Florence 27571, Italy (Engel) Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig 04107, Germany (Engel) LIFE - Leipzig Research Centre for Civilization Diseases, University of Leipzig, Leipzig 04103, Germany |
Issue Date: | 19-Jun-2023 | Copyright year: | 2023 | Publisher: | Springer Nature | Place of publication: | United Kingdom | Publication information: | British Journal of Cancer. 128(12) (pp 2283-2294), 2023. Date of Publication: 29 Jun 2023. | Journal: | British Journal of Cancer | Abstract: | Background: The distribution of ovarian tumour characteristics differs between germline BRCA1 and BRCA2 pathogenic variant carriers and non-carriers. In this study, we assessed the utility of ovarian tumour characteristics as predictors of BRCA1 and BRCA2 variant pathogenicity, for application using the American College of Medical Genetics and the Association for Molecular Pathology (ACMG/AMP) variant classification system. Method(s): Data for 10,373 ovarian cancer cases, including carriers and non-carriers of BRCA1 or BRCA2 pathogenic variants, were collected from unpublished international cohorts and consortia and published studies. Likelihood ratios (LR) were calculated for the association of ovarian cancer histology and other characteristics, with BRCA1 and BRCA2 variant pathogenicity. Estimates were aligned to ACMG/AMP code strengths (supporting, moderate, strong). Result(s): No histological subtype provided informative ACMG/AMP evidence in favour of BRCA1 and BRCA2 variant pathogenicity. Evidence against variant pathogenicity was estimated for the mucinous and clear cell histologies (supporting) and borderline cases (moderate). Refined associations are provided according to tumour grade, invasion and age at diagnosis. Conclusion(s): We provide detailed estimates for predicting BRCA1 and BRCA2 variant pathogenicity based on ovarian tumour characteristics. This evidence can be combined with other variant information under the ACMG/AMP classification system, to improve classification and carrier clinical management.Copyright © 2023, The Author(s). | DOI: | http://monash.idm.oclc.org/login?url=https://dx.doi.org/10.1038/s41416-023-02263-5 | PubMed URL: | 37076566 [https://www.ncbi.nlm.nih.gov/pubmed/?term=37076566] | URI: | https://repository.monashhealth.org/monashhealthjspui/handle/1/49855 | Type: | Article | Subjects: | genetic screening medical genetics molecular pathology ovary cancer ovary tumor BRCA1 protein BRCA2 protein |
Type of Clinical Study or Trial: | Observational study (cohort, case-control, cross sectional, or survey) |
| Appears in Collections: | Articles |
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