Ovarian cancer pathology characteristics as predictors of variant pathogenicity in BRCA1 and BRCA2 /

Denise G O’Mahony; Susan J Ramus; Melissa C Southey; Nicola S Meagher; Andreas Hadjisavvas; Esther M John; Ute Hamann; Evgeny N Imyanitov; Irene L Andrulis; Priyanka Sharma; Mary B Daly; Christopher R Hake; Jeffrey N Weitzel; Anna Jakubowska; Andrew K Godwin; Adalgeir Arason; Anita Bane; Jacques Simard; Penny Soucy; Maria A Caligo; Phuong L Mai; Kathleen B. M Claes; Manuel R Teixeira; Wendy K Chung; Conxi Lazaro; Peter J Hulick; Amanda E Toland; Inge Sokilde Pedersen; Marian J. E Mourits; Susan L Neuhausen; Ana Vega; Miguel de la Hoya; Heli Nevanlinna; Mallika Dhawan; Valentina Zampiga; Rita Danesi; Liliana Varesco; Viviana Gismondi; Valerio Gaetano Vellone; Paul A James; Ramūnas Janavičius; Liene Nikitina-Zake; Finn Cilius Nielsen; Thomas van Overeem Hansen; Tanja Pejovic; Ake Borg; Johanna Rantala; Kenneth Offit; Marco Montagna; Katherine L Nathanson; Susan M Domchek; Ana Osorio; María J García; Beth Y Karlan; Fabienne Lesueur; Anna De Fazio; David Bowtell; Lesley McGuffog; Goska Leslie; Michael T Parsons; Thilo Dörk; Lisa-Marie Speith; Elizabeth Santana dos Santos; Alexandre André B. A da Costa; Paolo Radice; Paolo Peterlongo; Laura Papi; Christoph Engel; Eric Hahnen; Rita K Schmutzler; Barbara Wappenschmidt; Douglas F Easton; Marc Tischkowitz; Christian F Singer; Yen Yen Tan; Alice S Whittemore; Weiva Sieh; James D Brenton; Drakoulis Yannoukakos; Florentia Fostira; Irene Konstantopoulou; Jana Soukupova; Michal Vocka; Georgia Chenevix-Trench; Paul D. P Pharoah; Antonis C Antoniou; David E Goldgar; Amanda B Spurdle; Kyriaki Michailidou

doi:10.1038/s41416-023-02263-5

Title	Ovarian cancer pathology characteristics as predictors of variant pathogenicity in BRCA1 and BRCA2 /
Authors	O’Mahony, Denise G ; Ramus, Susan J ; Southey, Melissa C ; Meagher, Nicola S ; Hadjisavvas, Andreas ; John, Esther M ; Hamann, Ute ; Imyanitov, Evgeny N ; Andrulis, Irene L ; Sharma, Priyanka ; Daly, Mary B ; Hake, Christopher R ; Weitzel, Jeffrey N ; Jakubowska, Anna ; Godwin, Andrew K ; Arason, Adalgeir ; Bane, Anita ; Simard, Jacques ; Soucy, Penny ; Caligo, Maria A ; Mai, Phuong L ; Claes, Kathleen B. M ; Teixeira, Manuel R ; Chung, Wendy K ; Lazaro, Conxi ; Hulick, Peter J ; Toland, Amanda E ; Pedersen, Inge Sokilde ; Mourits, Marian J. E ; Neuhausen, Susan L ; Vega, Ana ; de la Hoya, Miguel ; Nevanlinna, Heli ; Dhawan, Mallika ; Zampiga, Valentina ; Danesi, Rita ; Varesco, Liliana ; Gismondi, Viviana ; Vellone, Valerio Gaetano ; James, Paul A ; Janavičius, Ramūnas ; Nikitina-Zake, Liene ; Nielsen, Finn Cilius ; van Overeem Hansen, Thomas ; Pejovic, Tanja ; Borg, Ake ; Rantala, Johanna ; Offit, Kenneth ; Montagna, Marco ; Nathanson, Katherine L ; Domchek, Susan M ; Osorio, Ana ; García, María J ; Karlan, Beth Y ; Lesueur, Fabienne ; De Fazio, Anna ; Bowtell, David ; McGuffog, Lesley ; Leslie, Goska ; Parsons, Michael T ; Dörk, Thilo ; Speith, Lisa-Marie ; dos Santos, Elizabeth Santana ; da Costa, Alexandre André B. A ; Radice, Paolo ; Peterlongo, Paolo ; Papi, Laura ; Engel, Christoph ; Hahnen, Eric ; Schmutzler, Rita K ; Wappenschmidt, Barbara ; Easton, Douglas F ; Tischkowitz, Marc ; Singer, Christian F ; Tan, Yen Yen ; Whittemore, Alice S ; Sieh, Weiva ; Brenton, James D ; Yannoukakos, Drakoulis ; Fostira, Florentia ; Konstantopoulou, Irene ; Soukupova, Jana ; Vocka, Michal ; Chenevix-Trench, Georgia ; Pharoah, Paul D. P ; Antoniou, Antonis C ; Goldgar, David E ; Spurdle, Amanda B ; Michailidou, Kyriaki
DOI	10.1038/s41416-023-02263-5
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Is Part of	British journal of cancer.. London : Springer Nature. 2023, vol. 128, iss. 12, p. 2283-2294.. ISSN 0007-0920. eISSN 1532-1827
Abstract [eng]	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. Methods: 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). Results: 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. Conclusions: 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.
Published	London : Springer Nature
Type	Journal article
Language	English
Publication date	2023
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„Ovarian cancer pathology characteristics as predictors of variant pathogenicity in BRCA1 and BRCA2 /“