Causative Role for a BRCA2 Germline Pathogenic Variant in External Auditory Canal Squamous Cell Carcinoma

Genes Chromosomes Cancer. 2026 Apr;65(4):e70123. doi: 10.1002/gcc.70123.

Abstract

External auditory canal squamous cell carcinoma (EACSCC) is rare, affecting 1.6 in a million individuals. We report a case of EACSCC in a 66-year-old woman carrying a heterozygous BRCA2 germline pathogenic variant (GPV) (c.8537_8538del), with prior history of breast cancer. Tumor copy-number analysis showed loss of heterozygosity at the BRCA2 locus. Genomic scar analysis supported homologous recombination repair deficiency (HRD), with mutational signatures showing the predominance of APOBEC activity and lower contributions of HRD-associated single base (SBS3, SBS8) and INDEL (ID6) signatures. A somatic TP53 pathogenic variant was also identified. These findings suggest a contributory role for BRCA2 in EACSCC development.

Keywords: BRCA2; EACSCC; HRD; WES; mutational signatures.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • BRCA2 Protein* / genetics
  • Carcinoma, Squamous Cell* / genetics
  • Carcinoma, Squamous Cell* / pathology
  • Ear Canal / pathology
  • Ear Neoplasms* / genetics
  • Ear Neoplasms* / pathology
  • Female
  • Germ-Line Mutation*
  • Humans
  • Loss of Heterozygosity

Substances

  • BRCA2 Protein
  • BRCA2 protein, human

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