Whole-exome sequencing and RNA sequencing analyses of acinic cell carcinomas of the breast

Francisco Beca, Simon S.K. Lee, Fresia Pareja, Arnaud Da Cruz Paula, Pier Selenica, Lorenzo Ferrando, Rodrigo Gularte-Mérida, Hannah Y. Wen, Hong Zhang, Elena Guerini-Rocco, Emad A. Rakha, Britta Weigelt, Jorge S. Reis-Filho

Research output: Contribution to journalArticlepeer-review


Aims: Acinic cell carcinoma (ACC) of the breast is a rare histological form of triple-negative breast cancer (TNBC). Despite its unique histology, targeted sequencing analysis has failed to identify recurrent genetic alterations other than those found in common forms of TNBC. Here we subjected three breast ACCs to whole-exome and RNA sequencing to determine whether they would harbour a pathognomonic genetic alteration. Methods and results: DNA and RNA samples from three breast ACCs were subjected to whole-exome sequencing and RNA-sequencing, respectively. Somatic mutations, copy number alterations, mutational signatures and fusion genes were determined with state-of-the-art bioinformatics methods. Our analyses revealed TP53 hotspot mutations associated with loss of heterozygosity of the wild-type allele in two cases. Mutations affecting homologous recombination DNA repair-related genes were found in two cases, and an MLH1 pathogenic germline variant was found in one case. In addition, copy number analysis revealed the presence of a somatic BRCA1 homozygous deletion and focal amplification of 12q14.3–12q21.1, encompassing MDM2, HMGA2, FRS2, and PTPRB. No oncogenic in-frame fusion transcript was identified in the three breast ACCs analysed. Conclusions: No pathognomonic genetic alterations were detected in the breast ACCs analysed. These tumours have somatic genetic alterations similar to those of common forms of TNBC, and may show homologous recombination deficiency or microsatellite instability. These findings provide further insights into why breast ACCs, which are usually clinically indolent, may evolve into or in parallel with high-grade TNBC.

Original languageEnglish
Pages (from-to)931-937
Number of pages7
Issue number6
Publication statusPublished - Dec 1 2019


  • acinic cell carcinoma
  • breast cancer
  • DNA damage repair
  • massively parallel sequencing

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology


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