Development of breast tumors in CHEK2, NBN/NBS1 and BLM mutation carriers does not commonly involve somatic inactivation of the wild-type allele

被引:19
作者
Suspitsin, Evgeny N. [1 ,2 ]
Yanus, Grigory A. [1 ,2 ]
Sokolenko, Anna P. [1 ,2 ]
Yatsuk, Olga S. [1 ]
Zaitseva, Olga A. [1 ]
Bessonov, Alexandr A. [3 ]
Ivantsov, Alexandr O. [1 ]
Heinstein, Valeria A. [1 ,3 ]
Klimashevskiy, Valery F. [1 ]
Togo, Alexandr V. [1 ,2 ]
Imyanitov, Evgeny N. [1 ,2 ,4 ]
机构
[1] NN Petrov Oncol Res Inst, St Petersburg 197758, Russia
[2] St Petersburg Pediat Med Univ, St Petersburg 194100, Russia
[3] St Petersburg City Canc Ctr, St Petersburg 197758, Russia
[4] II Mechnikov North Western Med Univ, St Petersburg 191015, Russia
基金
俄罗斯基础研究基金会;
关键词
LOH; Somatic mutation; Two-hit model; CHEK2; NBN/NBS1; BLM; CANCER PATIENTS; GERMLINE MUTATIONS; 657DEL5; MUTATION; NBS1; GENE; BRCA1; CHEK2-ASTERISK-1100DELC; HETEROZYGOSITY; SUSCEPTIBILITY; CONTRIBUTE; FAMILIES;
D O I
10.1007/s12032-013-0828-9
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Somatic inactivation of the remaining allele is a characteristic feature of cancers arising in BRCA1 and BRCA2 mutation carriers, which determines their unprecedented sensitivity to some DNA-damaging agents. Data on tumor-specific status of the involved gene in novel varieties of hereditary breast cancer (BC) remain incomplete. We analyzed 32 tumors obtained from 30 patients with non-BRCA1/2 BC-associated germ-line mutations: 25 women were single mutation carriers (7 BLM, 15 CHEK2 and 3 NBN/NBS1) and 5 were double mutation carriers (2 BLM/BRCA1, 1 CHEK2/BLM, 1 CHEK2/BRCA1 and 1 NBN/BLM). Losses of heterozygosity affecting the wildtype allele were detected in none of the tumors from BLM mutation carriers, 3/18 (17 %) CHEK2-associated BC and 1/4 (25 %) NBN/NBS1-driven tumors. The remaining 28 BC were subjected to the sequence analysis of entire coding region of the involved gene; no somatic mutations were identified. We conclude that the tumor-specific loss of the wild-type allele is not characteristic for BC arising in CHEK2, NBN/NBS1 and BLM mutation carriers. Rarity of "second-hit'' inactivation of the involved gene in CHEK2-, NBN/NBS1- and BLM-associated BC demonstrates their substantial biological difference from BRCA1/2-driven cancers and makes them poorly suitable for the clinical trials with cisplatin and PARP inhibitors.
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页数:7
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