open access publication

Article, 2023

Genomic Landscape of Normal and Breast Cancer Tissues in a Hungarian Pilot Cohort

In: International Journal of Molecular Sciences, ISSN 1661-6596, 1422-0067, Volume 24, 10, Page 8553, 10.3390/ijms24108553

Contributors (14)

Pipek, Orsolya Anna (0000-0001-8109-0340) [1] Alpár, Donát (0000-0002-2638-5418) [2] Rusz, Orsolya [2] Bödör, Csaba (0000-0002-0729-692X) [2] Udvarnoki, Zoltán [1] Medgyes-Horváth, Anna (0000-0003-4435-5797) [1] Csabai, István Ervin (0000-0001-9232-9898) [1] Szallasi, Zoltan Imre (0000-0001-5395-7509) [2] [3] [4] [5] Madaras, Lilla [2] Kahán, Zsuzsanna [6] Cserni, Gábor (0000-0003-1344-7744) [6] [7] Kovari, Bence (0000-0003-1555-640X) [6] [8] Kulka, Janina (0000-0001-8884-8337) [2] Tőkés, Anna-Mária (0000-0002-9581-7536) (Corresponding author) [2]


  1. [1] Eötvös Loránd University
  2. [NORA names: Hungary; Europe, EU; OECD]
  3. [2] Semmelweis University
  4. [NORA names: Hungary; Europe, EU; OECD]
  5. [3] Boston Children's Hospital
  6. [NORA names: United States; America, North; OECD]
  7. [4] Danish Cancer Society
  8. [NORA names: DCRC Danish Cancer Society Research Center; Non-Profit Organizations; Denmark; Europe, EU; Nordic; OECD]
  9. [5] Harvard University
  10. [NORA names: United States; America, North; OECD]


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.


DNA levels, Europe, European populations, Hungary, alterations, aspects, breast cancer, breast cancer cohort, breast cancer patient population, breast cancer patients, breast cancer tissues, cancer, cancer cohort, cancer patient population, cancer patients, cancer tissues, characterization, cohort, comprehensive genomic characterization, copy number variations, data, database, deficiency, deletion, different ethnic populations, ethnic groups, ethnic populations, events, fusion events, genes, genomic characterization, genomic landscape, germline mutations, group, homologous recombination deficiency, independent European populations, insertion, landscape, levels, limited number, majority, multiple signs, mutational landscape, mutational processes, mutational signatures, mutations, normals, number, number alterations, number variations, pathogenic germline mutations, patient population, patients, pilot cohort, polymorphism, population, process, recombination deficiency, samples, sequencing, sequencing studies, short variant, signatures, signs, single nucleotide polymorphisms, somatic mutational landscape, somatic mutations, study, subset, tissue, values, variants, variation, whole-genome sequencing


  • National Research, Development and Innovation Office
  • Hungarian Academy of Sciences
  • European Commission