Abstract 1241: Profile of BRCA1/BRCA2 mutations in Russian ovarian cancer population detected by NGS and MLPA analysis: Interim results of OVATAR study
Authors: Tyulyandina Alexandra , Gorbunova Vera , Khokhlova Svetlana , Kolomiets Larisa , Filipenko Maksim , Imyanitov Evgeny , Demidova Irina , Moliaka Yuri , Cherdyntseva Nadezhda , Vodolajskiy Dmitriy , Lyubchenko Ludmila , Tjulandin Sergei , Tsimafeyeu Ilya , Vedrova Olga , Karaseva Vera , Andreev Sergei , Kekeeva Tatiana 
Published: August 2018

Abstract
Background: This study is a first attempt to determine frequency of gBRCAm and share of sBRCAm in Russian ovarian cancer (OC) cancer patients (pts) using next-generation sequencing (NGS) and multiplex ligation-dependent probe amplification (MLPA). Russian population is known to have a sizable proportion of “frequent” germline mutations in BRCA genes, with occurrence in &gt;2% of all BRCAm cases.
Methods: 498 pts with primary serous and endometrioid OC were enrolled in noninterventional study OVATAR (NCT02122588). NGS testing of BRCAm in genomic DNA (gDNA) from leukocytes and primary tumor tissue was performed. MLPA assay for large rearrangements (LGR) was used on gDNA from leukocytes.
Results: Interim analysis includes pairs of tumor and blood samples from 400 pts. The total rate of BRCA1/2 mutations was 35% (140/400 pts) including 29.8% (119/400) of germline mutations (gBRCAm) and 5.2% (21/400) of somatic mutations. Alterations reported hereby were either classified as deleterious/pathogenic in public databases, or identified as “likely pathogenic” (e.g., loss-of-function). VUS were not included. Frequent gBRCAm were detected in 49.3% of gBRCAm cases (69/140). BRCAm were counted as rare: in 30.7% (43/140) pts, including LGR in 3.6% (5/140) pts. sBRCAm: in 15% (21/140) pts. Although previously counted as frequent, 6174delT in BRCA2 was not detected. 4 pts carried pathogenic germline BRCA2 c.T5286G:p.Y1762* nonsense mutation, with prevalence 2.9% among BRCAm carriers, which makes it the new and only potential “hot-spot” in BRCA2 gene. Large deletions comprise 5% of all BRCAm and mostly occur in BRCA1 gene.
Conclusion: The overall rate of both somatic and germline BRCA variations in Russian OC population is in line with global data, with high percent of 8 frequent gBRCAm (49.3%). Use of MLPA is limited by blood samples with low rate of germline LGR. NGS is becoming a method of choice to hit both small variations and LGR in BRCA genes.
gene/mutation# of pts (n=140) and % of BRCAmgBRCAmFrequent mutations n=69 (49,3%)BRCA15382insC3726,4%4154delA75,0%2080delA64,3%C61G53,6%185delAG42,9%3819del532,1%3875del432,1%BRCA2T5286G (c.T5286G:p.Y1762*)42,9%Rare mutations n=43 (30,7%)BRCA12417,1%BRCA21913,6%Exons deletions n=7 (5%)BRCA164,3%BRCA210,7%sBRCAmn=21 (15%)BRCA1139,3%BRCA285,7%
Citation Format: Alexandra Tyulyandina, Vera Gorbunova, Svetlana Khokhlova, Larisa Kolomiets, Maksim Filipenko, Evgeny Imyanitov, Irina Demidova, Yuri Moliaka, Nadezhda Cherdyntseva, Dmitriy Vodolajskiy, Ludmila Lyubchenko, Sergei Tjulandin, Ilya Tsimafeyeu, Olga Vedrova, Vera Karaseva, Sergei Andreev, Tatiana Kekeeva. Profile of BRCA1/BRCA2 mutations in Russian ovarian cancer population detected by NGS and MLPA analysis: Interim results of OVATAR study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1241.