Ethnicity-specific BRCA1, BRCA2, PALB2, and ATM pathogenic alleles in breast and ovarian cancer patients from the North Caucasus.
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Sokolenko Anna P, Bakaeva Elvina Kh, Venina Aigul R, Kuligina Ekaterina Sh, Romanko Alexandr A, Aleksakhina Svetlana N, Belysheva Yana V, Belogubova Evgeniya V, Stepanov Ilya A, Zaitseva Olga A, Yatsuk Olga S, Togo Alexandr V, Khamgokov Zaur M, Kadyrova Azinat O, Pirmagomedov Albert Sh, Bolieva Marina B, Epkhiev Alexandr A, Tsutsaev Aslan K, Chakhieva Madina D, Khabrieva Khalimat M, Khabriev Idris M, Murachuev Mirza A, Buttaeva Bella N, Baboshkina Liliya S, Bayramkulova Fatima I, Katchiev Islam R, Alieva Lina Kh, Raskin Grigory A, Orlov Sergey V, Khachmamuk Zarema K, Levonyan Karine R, Gichko Dariya M, Kirtbaya Dmitriy V, Degtyariov Alexey M, Sultanova Luisa V, Musayeva Hedi S, Belyaev Alexey M, Imyanitov Evgeny N
Аннотация
METHODS: This study involved high-grade serous ovarian cancer (HGSOC) and breast cancer (BC) patients from Dagestan (HGSOC: 37; BC: 198), Kabardino-Balkaria (HGSOC: 68; BC: 155), North Ossetia (HGSOC: 51; BC: 104), Chechnya (HGSOC: 68; BC: 79), Ingushetia (HGSOC: 19; BC: 103), Karachay-Cherkessia (HGSOC: 13; BC: 47), and several Armenian settlements (HGSOC: 16; BC: 101). The group of BC patients was enriched by young-onset and/or family history-positive and/or bilateral and/or receptor triple-negative cases. The entire coding region of BRCA1, BRCA2, PALB2, and ATM genes was analyzed by next-generation sequencing.
RESULTS: A significant contribution of BRCA1/2 pathogenic variants (PVs) to HGSOC and BC development was observed across all North Caucasus regions (HGSOC: 19-39%; BC: 6-13%). Founder alleles were identified in all ethnic groups studied, e.g., BRCA1 c.3629_3630delAG in Chechens, BRCA2 c.6341delC in North Ossetians, BRCA2 c.5351dupA in Ingush, and BRCA1 c.2907_2910delTAAA in Karachays. Some BRCA1/2 alleles, particularly BRCA2 c.9895C > T, were shared by several nationalities. ATM PVs were detected in 14 patients, with c.1673delG and c.8876_8879delACTG alleles occurring twice each. PALB2 heterozygosity was observed in 5 subjects, with one variant seen in 2 unrelated women.
CONCLUSION: This study adds to the evidence for the global-wide contribution of BRCA1/2 genes to HGSOC and BC morbidity, although the spectrum of their PVs is a subject of ethnicity-specific variations. The data on founder BRCA1/2 alleles may be considered when adjusting the BRCA1/2 testing procedure to the ethnic origin of patients.