K Rust1, P Spiliopoulou2, C Y Tang3, C Bell4, D Stirling5, Thf Phang6, R Davidson7, M Mackean1, F Nussey1, R M Glasspool2, N S Reed2, A Sadozye2, M Porteous5, T McGoldrick8, M Ferguson3, Z Miedzybrodzka4,6, I A McNeish2,9, C Gourley1,10. 1. Edinburgh Cancer Centre, Edinburgh, UK. 2. Beatson West of Scotland Cancer Centre, Glasgow, UK. 3. Department of Oncology, Ninewells Hospital, Dundee, UK. 4. Department of Medical Genetics, NHS Grampian, Aberdeen, UK. 5. Department of Clinical Genetics, Western General Hospital, Edinburgh, UK. 6. School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, UK. 7. Department of Genetics, Queen Elizabeth University Hospital, Glasgow, UK. 8. Department of Oncology, Aberdeen Royal Infirmary, Aberdeen, UK. 9. Institute of Cancer Sciences, University of Glasgow, Glasgow, UK. 10. Nicola Murray Centre for Ovarian Cancer Research, University of Edinburgh Cancer Research UK Centre, MRC IGMM, Western General Hospital, Edinburgh, UK.
Abstract
OBJECTIVE: To determine the rates of germline BRCA1 and BRCA2 mutations in Scottish patients with ovarian cancer, before and after a change in testing policy. DESIGN: Retrospective cohort study. SETTING: Four cancer/genetics centres in Scotland. POPULATION: Patients with ovarian cancer undergoing germline BRCA1 and BRCA2 (gBRCA1/2) sequencing before 2013 (under the 'old criteria', with selection based solely on family history), after 2013 (under the 'new criteria', with sequencing offered to newly presenting patients with non-mucinous ovarian cancer), and in the 'prevalent population' (who presented before 2013, but were not eligible for sequencing under the old criteria but were sequenced under the new criteria). METHODS: Clinicopathological and sequence data were collected before and for 18 months after this change in selection criteria. MAIN OUTCOME MEASURES: Frequency of germline BRCA1, BRCA2, RAD51C, and RAD51D mutations. RESULTS: Of 599 patients sequenced, 205, 236, and 158 were in the 'old criteria', 'new criteria', and 'prevalent' populations, respectively. The frequency of gBRCA1/2 mutations was 30.7, 13.1, and 12.7%, respectively. The annual rate of gBRCA1/2 mutation detection was 4.2 before and 20.7 after the policy change. A total of 48% (15/31) 'new criteria' patients with gBRCA1/2 mutations had a Manchester score of <15 and would not have been offered sequencing based on family history criteria. In addition, 20 patients with gBRCA1/2 were identified in the prevalent population. The prevalence of gBRCA1/2 mutations in patients aged >70 years was 8.2%. CONCLUSIONS: Sequencing all patients with non-mucinous ovarian cancer gives a much higher annual gBRCA1/2 mutation detection rate, with the frequency of positive tests still exceeding the 10% threshold upon which many family history-based models operate. TWEETABLE ABSTRACT: BRCA sequencing all non-mucinous cancer patients increases mutation detection five fold.
OBJECTIVE: To determine the rates of germline BRCA1 and BRCA2 mutations in Scottish patients with ovarian cancer, before and after a change in testing policy. DESIGN: Retrospective cohort study. SETTING: Four cancer/genetics centres in Scotland. POPULATION: Patients with ovarian cancer undergoing germline BRCA1 and BRCA2 (gBRCA1/2) sequencing before 2013 (under the 'old criteria', with selection based solely on family history), after 2013 (under the 'new criteria', with sequencing offered to newly presenting patients with non-mucinous ovarian cancer), and in the 'prevalent population' (who presented before 2013, but were not eligible for sequencing under the old criteria but were sequenced under the new criteria). METHODS: Clinicopathological and sequence data were collected before and for 18 months after this change in selection criteria. MAIN OUTCOME MEASURES: Frequency of germline BRCA1, BRCA2, RAD51C, and RAD51D mutations. RESULTS: Of 599 patients sequenced, 205, 236, and 158 were in the 'old criteria', 'new criteria', and 'prevalent' populations, respectively. The frequency of gBRCA1/2 mutations was 30.7, 13.1, and 12.7%, respectively. The annual rate of gBRCA1/2 mutation detection was 4.2 before and 20.7 after the policy change. A total of 48% (15/31) 'new criteria' patients with gBRCA1/2 mutations had a Manchester score of <15 and would not have been offered sequencing based on family history criteria. In addition, 20 patients with gBRCA1/2 were identified in the prevalent population. The prevalence of gBRCA1/2 mutations in patients aged >70 years was 8.2%. CONCLUSIONS: Sequencing all patients with non-mucinous ovarian cancer gives a much higher annual gBRCA1/2 mutation detection rate, with the frequency of positive tests still exceeding the 10% threshold upon which many family history-based models operate. TWEETABLE ABSTRACT: BRCA sequencing all non-mucinous cancer patients increases mutation detection five fold.
Authors: Hasan Mirza; Darren P Ennis; Zhao Cheng; Philip Smith; Lena Morrill Gavarró; Chishimba Sokota; Gaia Giannone; Theodora Goranova; Thomas Bradley; Anna Piskorz; Michelle Lockley; Baljeet Kaur; Naveena Singh; Laura A Tookman; Jonathan Krell; Jacqueline McDermott; Geoffrey Macintyre; Florian Markowetz; James D Brenton; Iain A McNeish Journal: Clin Cancer Res Date: 2022-07-01 Impact factor: 13.801
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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