Next generation sequencing analysis of key genes in breast cancer patients from Kazakh population.

A. Zh. Abdrakhmanova, Nazgul Omarbayeva, Dilyara Kaidarova, Gulnur Zhunussova, Saltanat Abdikerim, Saule Yessenkulova, Aizhan Jakipbayeva, Zhanna K. Chingissova, Leila Djansugurova

2020

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DOI 10.1200/jco.2020.38.15_suppl.e13548
Data confidence 70 medium
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Abstract

e13548 Background: Breast cancer (BC) shows a high incidence both in Kazakhstan and worldwide. Approximately 20-30% of cases of hereditary breast cancer are caused by presence of BRCA1/2 genes defects. Also, there are additional genes, which can increase the risk of BC and they are still under study. In our study we identify new, detectable and objective markers of key cancer genes by next-generation sequencing (NGS) of young BC patients in Kazakh population. Methods: The study enrolled 235 unrelated patients from Kazakh population(the average age 34.25 ± 4.56) with BC. Genomic DNA was obtained from peripheral blood and sequencing was performed using TruSight Cancer Kit on the MiSeq platform. Studio Variant was used to annotate and interpret genetic variants. 26(11.1%) patients had a maternal family history of BC, 21 (80.8%) of them had first- degree relatives diagnosed with BC at different age. Results: Bioinformatics analysis of NGS data identified 23,915 variants in 83 genes. 64 pathogenic variants in the heterozygous state were found in 62 (26.4%) patients, 8 (12.5%) variants were not previously described in databases (LOVD, ClinVar, 1000 Genomes, ESP6500 and ExAC). The most frequent pathogenic mutations were in the genes BRCA1 (24 variants (37.5%) and BRCA2 (18 (28.1%)). Additional pathogenic variants were identified in the non-BRCA genes (APC, ATM, BLM, CHEK2, PALB2, TP53, ERCC2, FANCA, FANCM, NBN, PMS1, PMS2, SDHB and XPA). A hereditary history was recorded in 29.1% and 27.8% of representatives of the group with pathogenic mutations in the BRCA1 and BRCA2, respectively, higher compared to the group of patients without pathogenic mutations and to the group of patients with non-BRCA genes. Conclusions: The frequent and novel germline mutations in BRCA1/2 and non-BRCA genes were identified by NGS. Diagnostic and prevention tools for key genes are considered to be developed and included in the National guidelines of Republic of Kazakhstan after final statistic data processing.