Molecular genetic investigation of hereditary breast and ovarian cancer patients in the Southern Transdanubian region: widening the mutation spectrum and searching for new pathogenic variants using next-generation methods

Pathol Oncol Res. 2024 Aug 1:30:1611813. doi: 10.3389/pore.2024.1611813. eCollection 2024.

Abstract

Hereditary breast and ovarian cancer is a well-known genetic condition, inherited mainly in an autosomal dominant way, which elevates the risk of developing malignancies at a young age in heterozygous carriers. Advances in new generation sequencing have enabled medical professionals to determine whether a patient is harbouring mutations in moderate- or high penetrance susceptibility genes. We conducted a retrospective analysis among 275 patients who underwent genetic counselling and multigene panel testing for hereditary breast and ovarian cancer syndrome in our department. From these patients 74.5% (205/275) were affected by some type of malignancy, while the remaining 25.5% (70/275) had a positive family history of different cancers, suggesting a genetic predisposition. These tests confirmed a genetic variant in 29.8% and 28.6% of these patient groups respectively. The results also mirrored our general knowledge concerning the genetic background of hereditary breast and ovarian cancer, as variants in either one of the BRCA1 and BRCA2 genes proved to be the most common cause among our patients with 41.5%. Our test also detected a novel mutation in the CDH1 gene and three patients with double heterozygosity in two different susceptibility genes. This study demonstrates the relevance of genetic counselling and non-BRCA gene sequencing among cancer patients and patients who fulfil the criteria for genetic testing, while also providing important details about the genetic profile of Hungarian patients.

Keywords: BRCA1; BRCA2; HBOC; multigene panel testing; new generation sequencing.

MeSH terms

  • Adult
  • Aged
  • Antigens, CD
  • BRCA1 Protein* / genetics
  • BRCA2 Protein* / genetics
  • Biomarkers, Tumor / genetics
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology
  • Cadherins
  • Female
  • Genetic Counseling
  • Genetic Predisposition to Disease*
  • Genetic Testing / methods
  • Hereditary Breast and Ovarian Cancer Syndrome / genetics
  • High-Throughput Nucleotide Sequencing* / methods
  • Humans
  • Middle Aged
  • Mutation*
  • Ovarian Neoplasms* / genetics
  • Ovarian Neoplasms* / pathology
  • Retrospective Studies
  • Young Adult

Substances

  • BRCA2 Protein
  • BRCA2 protein, human
  • BRCA1 protein, human
  • BRCA1 Protein
  • Biomarkers, Tumor
  • CDH1 protein, human
  • Antigens, CD
  • Cadherins

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work is supported (not financially) by the European Reference Network on Genetic Tumour Risk Syndromes (ERN GENTURIS). This study was supported by the Medical School of the University of Pécs, “ÁOK-KA” Research Program; KA-2023-22.