TY - JOUR ID - 90156 TI - Pathogenicity Reclassification of Genetic Variants Related to Early-Onset Breast Cancer among Women of Mongoloid Origin JO - Asian Pacific Journal of Cancer Prevention JA - APJCP LA - en SN - 1513-7368 AU - Gervas, Polina AU - Molokov, Aleksey AU - Babyshkina, Nataliya AU - Kiselev, Artem AU - Zarubin, Aleksei AU - Yumov, Evgeny AU - Pisareva, Lubov AU - Choynzonov, Evgeny AU - Cherdyntseva, Nadezda AD - Department of Molecular oncology and Immunology, Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Science, Tomsk, Russia. AD - Almazov National Medical Research Centre, St. Petersburg, Russia. AD - Research Institute of Medical Genetics, Tomsk National Research Medical Center, Russian Academy of Science, Tomsk, Russia AD - Department of Surgery, GBUZ “Buryat Republican clinical oncology dispensary”, Republic of Buryatia, Ulan-Ude, Russia. Y1 - 2022 PY - 2022 VL - 23 IS - 6 SP - 2027 EP - 2033 KW - VUS KW - breast cancer KW - Mongoloid race KW - Central Asia DO - 10.31557/APJCP.2022.23.6.2027 N2 - Background: Germline alterations in BRCA1, BRCA2, and other genes are responsible for early-onset breast cancer. However, up to 20% of molecular tests report genetic variant of unknown significance (VUS) or novel variants that have never been previously described and their clinical significance are unknown. This study aimed to reclassify variant of unknown significance (VUS) or novel variants by using the ActiveDriveDB database that annotates variants through the lens of sites of post-translational modifications (PTM). Methods: Our study included thirty-eighth young Buryat BC patients, belonging to the Mongoloid race and anthropologically to the Central Asia. Genomic DNA was extracted from the peripheral blood lymphocytes using the phenol/chloroform method. DNA library were prepared using the Hereditary Cancer SolutionTM kit (Sophia GENETICS, Switzerland) to cover 27 genes, such as ATM, APC, BARD1, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, EPCAM, FAM175A, MLH1, MRE11A, MSH2, MSH6, MUTYH, NBN, PALB2, PIK3CA, PMS2, PMS2CL, PTEN, RAD50, RAD51C, RAD51D, STK11, TP53, and XRCC2. Paired-end sequencing (2 x 150 bp) was conducted using NextSeq 500 system (Illumina, USA). Results: We re-examined 135 rare variants (41 VUS, 25 conflicting, 64 benign and 5 new variants). We identified 10 out of 135 (7.4%) mutations that affected the sites of post-translational modification in proteins. Of 135 rare mutations, 1 benign variant was reclassified as network-rewiring - motif loss mutation, 3 VUS and 1 new variant were reclassified as distal PTM- mutations, 2 new and 1 benign variant were classified as proximal PTM- mutations and 1 benign and 1 conflicting variant were classified as direct PTM- mutations.Conclusions: For the first time, 7.4% (10 out of 135) of mutations that affected the sites of post-translational modification in proteins were identified among early-onset breast cancer women of Mongoloid origin. UR - https://journal.waocp.org/article_90156.html L1 - https://journal.waocp.org/article_90156_78a30b57c2923326357b556fc2c82cda.pdf ER -