János Bolyai Research Scholarship of the Hungarian Academy of Sciences(TKP2021-NVA-15)
(NVKP-16-1-2016-0004)
(739593) Támogató: Horizon 2020
(BO/00125/22)
(ÚNKP-22-5-SE-7)
Az orvos-, egészségtudományi- és gyógyszerészképzés tudományos műhelyeinek fejlesztése(EFOP-3.6.3-VEKOP-16-2017-00009)
Támogató: EFOP-VEKOP
Szakterületek:
Patológia
A limited number of studies have focused on the mutational landscape of breast cancer
in different ethnic populations within Europe and compared the data with other ethnic
groups and databases. We performed whole-genome sequencing of 63 samples from 29 Hungarian
breast cancer patients. We validated a subset of the identified variants at the DNA
level using the Illumina TruSight Oncology (TSO) 500 assay. Canonical breast-cancer-associated
genes with pathogenic germline mutations were CHEK2 and ATM. Nearly all the observed
germline mutations were as frequent in the Hungarian breast cancer cohort as in independent
European populations. The majority of the detected somatic short variants were single-nucleotide
polymorphisms (SNPs), and only 8% and 6% of them were deletions or insertions, respectively.
The genes most frequently affected by somatic mutations were KMT2C (31%), MUC4 (34%),
PIK3CA (18%), and TP53 (34%). Copy number alterations were most common in the NBN,
RAD51C, BRIP1, and CDH1 genes. For many samples, the somatic mutational landscape
was dominated by mutational processes associated with homologous recombination deficiency
(HRD). Our study, as the first breast tumor/normal sequencing study in Hungary, revealed
several aspects of the significantly mutated genes and mutational signatures, and
some of the copy number variations and somatic fusion events. Multiple signs of HRD
were detected, highlighting the value of the comprehensive genomic characterization
of breast cancer patient populations.
