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Vol 55(2021) N 3 p. 354-362; DOI 10.1134/S0026893321020163 Full Text

I.S. Abramov1, Yu.S. Korneva2, O.A. Shisterova3, A.Yu. Ikonnikova1, M.A. Emelyanova1, T.S. Lisitsa1, G.S. Krasnov1, T.V. Nasedkina1*

Germline and Somatic Mutations in Archived Breast Cancer Specimens of Different Subtypes

1Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991 Russia
2Smolensk State Medical University, Smolensk, 214019 Russia
3Smolensk Regional Clinical Oncologic Dispensary, Smolensk, 214000 Russia

*nased@biochip.ru
Received - 2020-09-02; Revised - 2020-09-25; Accepted - 2020-09-29

Molecular profiling of tumors may provide promising options for personalized treatment. We have examined the spectrum of germline and somatic mutations in 23 breast cancers (ВС) of various molecular subtypes, including tumors 1) with expression of estrogen, progesterone and/or epidermal growth factor receptor HER2/neu, and 2) with a triple negative phenotype. Genomic DNA specimens were isolated from archived tumor and normal tissue samples and subjected to targeted sequencing of the coding regions of 25 cancer-associated genes with a mean coverage of x 1000. In the triple negative subtype of ВС, the pathogenic germline mutations BRCA1 c.66_67delAG (185delAG) and BRCA1 c.3226_3227AG (3347delAG) were detected, while the germline mutation BRCA2 658_659del (886delGT) was found in patients with positive receptor staining. Mutations in BRCAl/2 were overrepresented by frequency (80%), pointing at common loss of heterozygosity affecting the normal allele. Somatic mutations in the TP53 gene were found in 7/10 (70%) patients with the triple negative subtype of ВС and in 3/13 (23%) in the group with positive receptor staining. Additionally, in both groups of patients, somatic mutations of the PTEN, MSH2, MSH6, and MUTYH genes were detected.

breast cancer, triple negative subtype, archived tumor specimens, targeted sequencing, germline and somatic mutations



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