| Autor: |
Pipek O; Department of Physics of Complex Systems, Institute of Physics, Eötvös Loránd University, 1117 Budapest, Hungary., Alpár D; HCEMM-SE Molecular Oncohematology Research Group, Department of Pathology and Experimental Cancer Research, Semmelweis University, 1085 Budapest, Hungary., Rusz O; Department of Pathology, Forensic and Insurance Medicine, SE NAP, Brain Metastasis Research Group, Semmelweis University, 1091 Budapest, Hungary., Bödör C; HCEMM-SE Molecular Oncohematology Research Group, Department of Pathology and Experimental Cancer Research, Semmelweis University, 1085 Budapest, Hungary., Udvarnoki Z; Department of Physics of Complex Systems, Institute of Physics, Eötvös Loránd University, 1117 Budapest, Hungary., Medgyes-Horváth A; Department of Physics of Complex Systems, Institute of Physics, Eötvös Loránd University, 1117 Budapest, Hungary., Csabai I; Department of Physics of Complex Systems, Institute of Physics, Eötvös Loránd University, 1117 Budapest, Hungary., Szállási Z; Department of Pathology, Forensic and Insurance Medicine, SE NAP, Brain Metastasis Research Group, Semmelweis University, 1091 Budapest, Hungary.; Computational Health Informatics Program (CHIP), Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.; Danish Cancer Society Research Center, 2100 Copenhagen, Denmark., Madaras L; Department of Pathology, Forensic and Insurance Medicine, Semmelweis University, 1091 Budapest, Hungary., Kahán Z; Department of Oncotherapy, University of Szeged, 6720 Szeged, Hungary., Cserni G; Department of Pathology, Albert Szent-Györgyi Medical Centre, University of Szeged, 6720 Szeged, Hungary.; Department of Pathology, Bács-Kiskun County Teaching Hospital, 6000 Kecskemét, Hungary., Kővári B; Department of Pathology, Albert Szent-Györgyi Medical Centre, University of Szeged, 6720 Szeged, Hungary.; Department of Pathology, Henry Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA., Kulka J; Department of Pathology, Forensic and Insurance Medicine, Semmelweis University, 1091 Budapest, Hungary., Tőkés AM; Department of Pathology, Forensic and Insurance Medicine, Semmelweis University, 1091 Budapest, Hungary. |
| Abstrakt: |
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. |
