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

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Abstract—

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 (BC) 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 ×1000. In the triple negative subtype of BC, 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 BRCA1/2 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 BC 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.

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Funding

This study was supported by the Federal Target Program “Research and Development in Priority Areas of Development of the Russian Scientific and Technological Complex for 2014–2020” (agreement No. 05.604.21.0234, unique project identifier RFMEFI60419X0234).

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Authors and Affiliations

  1. Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991, Moscow, Russia

    I. S. Abramov, A. Yu. Ikonnikova, M. A. Emelyanova, T. S. Lisitsa, G. S. Krasnov & T. V. Nasedkina

  2. Smolensk State Medical University, 214019, Smolensk, Russia

    Yu. S. Korneva

  3. Smolensk Regional Clinical Oncologic Dispensary, 214000, Smolensk, Russia

    O. A. Shisterova

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  1. I. S. Abramov
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Correspondence to T. V. Nasedkina.

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Statement of compliance with standards of research involving humans as subjects. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants involved in the study.

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Translated by M. Novikova

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Abramov, I.S., Korneva, Y.S., Shisterova, O.A. et al. Germline and Somatic Mutations in Archived Breast Cancer Specimens of Different Subtypes. Mol Biol 55, 354–362 (2021). https://doi.org/10.1134/S0026893321020163

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