OBJECTIVE: The recognition of genes implicated in ovarian cancer risk beyond BRCA1, BRCA2, and the Lynch syndrome genes has increased the variety of testing options available to providers and patients. We report the frequency of pathogenic variants identified among individuals with ovarian cancer undergoing clinical genetic testing via a multi-gene hereditary cancer panel. METHODS: Genetic testing of up to 32 genes using a hereditary cancer panel was performed on 4439 ovarian cancer cases, and results were analyzed for frequency of pathogenic variants. Statistical comparisons were made using t-tests and Fisher's exact tests. RESULTS: The positive yield was 13.2%. While BRCA1/2 pathogenic variants were most frequent, one third (33.7%) of positive findings were in other homologous recombination genes, and accounted for over 40.0% of findings in endometrioid and clear cell cases. Women with a personal history of breast cancer (22.1%), who reported a family history of ovarian cancer (17.7%), and/or serous histology (14.7%) were most likely to harbor a pathogenic variant. Those with very early onset (<30 years) and late onset (≥70 years) ovarian cancer had low positive yields. CONCLUSIONS: Our study highlights the genetic heterogeneity of ovarian cancer, showing that a large proportion of cases are not due to BRCA1/2 and the Lynch syndrome genes, but still have an identifiable hereditary basis. These findings substantiate the utility of multi-gene panel testing in ovarian cancer care regardless of age at diagnosis, family history, or histologic subtype, providing evidence for testing beyond BRCA1/2 and the Lynch syndrome genes.
OBJECTIVE: The recognition of genes implicated in ovarian cancer risk beyond BRCA1, BRCA2, and the Lynch syndrome genes has increased the variety of testing options available to providers and patients. We report the frequency of pathogenic variants identified among individuals with ovarian cancer undergoing clinical genetic testing via a multi-gene hereditary cancer panel. METHODS: Genetic testing of up to 32 genes using a hereditary cancer panel was performed on 4439 ovarian cancer cases, and results were analyzed for frequency of pathogenic variants. Statistical comparisons were made using t-tests and Fisher's exact tests. RESULTS: The positive yield was 13.2%. While BRCA1/2 pathogenic variants were most frequent, one third (33.7%) of positive findings were in other homologous recombination genes, and accounted for over 40.0% of findings in endometrioid and clear cell cases. Women with a personal history of breast cancer (22.1%), who reported a family history of ovarian cancer (17.7%), and/or serous histology (14.7%) were most likely to harbor a pathogenic variant. Those with very early onset (<30 years) and late onset (≥70 years) ovarian cancer had low positive yields. CONCLUSIONS: Our study highlights the genetic heterogeneity of ovarian cancer, showing that a large proportion of cases are not due to BRCA1/2 and the Lynch syndrome genes, but still have an identifiable hereditary basis. These findings substantiate the utility of multi-gene panel testing in ovarian cancer care regardless of age at diagnosis, family history, or histologic subtype, providing evidence for testing beyond BRCA1/2 and the Lynch syndrome genes.
Authors: Kevin J Arvai; Maegan E Roberts; Rebecca I Torene; Lisa R Susswein; Megan L Marshall; Zhancheng Zhang; Natalie J Carter; Lauren Yackowski; Erica S Rinella; Rachel T Klein; Kathleen S Hruska; Kyle Retterer Journal: Hered Cancer Clin Pract Date: 2019-07-15 Impact factor: 2.857
Authors: Rachel Hodan; Kerry Kingham; Kristina Cotter; Ann K Folkins; Allison W Kurian; James M Ford; Teri Longacre Journal: Cancer Med Date: 2020-12-25 Impact factor: 4.452
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Authors: Klara Lhotova; Lenka Stolarova; Petra Zemankova; Michal Vocka; Marketa Janatova; Marianna Borecka; Marta Cerna; Sandra Jelinkova; Jan Kral; Zuzana Volkova; Marketa Urbanova; Petra Kleiblova; Eva Machackova; Lenka Foretova; Jana Hazova; Petra Vasickova; Filip Lhota; Monika Koudova; Leona Cerna; Spiros Tavandzis; Jana Indrakova; Lucie Hruskova; Marcela Kosarova; Radek Vrtel; Viktor Stranecky; Stanislav Kmoch; Michal Zikan; Libor Macurek; Zdenek Kleibl; Jana Soukupova Journal: Cancers (Basel) Date: 2020-04-13 Impact factor: 6.639