The repertoire of somatic genetic alterations of acinic cell carcinomas of the breast: An exploratory, hypothesis-generating study

Elena Guerini-Rocco, Zsolt Hodi, Salvatore Piscuoglio, Charlotte K Y Ng, Emad A. Rakha, Anne M. Schultheis, Caterina Marchiò, Arnaud Da Cruz Paula, Maria R. De Filippo, Luciano G. Martelotto, Leticia De Mattos-Arruda, Marcia Edelweiss, Achim A. Jungbluth, Nicola Fusco, Larry Norton, Britta Weigelt, Ian O. Ellis, Jorge S. Reis-Filho

Research output: Contribution to journalArticlepeer-review


Acinic cell carcinoma (ACC) of the breast is a rare form of triple-negative (that is, oestrogen receptor-negative, progesterone receptor-negative, HER2-negative) salivary gland-type tumour displaying serous acinar differentiation. Despite its triple-negative phenotype, breast ACCs are reported to have an indolent clinical behaviour. Here, we sought to define whether ACCs have a mutational repertoire distinct from that of other triple-negative breast cancers (TNBCs). DNA was extracted from microdissected formalin-fixed, paraffin-embedded sections of tumour and normal tissue from two pure and six mixed breast ACCs. Each tumour component of the mixed cases was microdissected separately. Tumour and normal samples were subjected to targeted capture massively parallel sequencing targeting all exons of 254 genes, including genes most frequently mutated in breast cancer and related to DNA repair. Selected somatic mutations were validated by targeted amplicon resequencing and Sanger sequencing. Akin to other forms of TNBC, the most frequently mutated gene found in breast ACCs was TP53 (one pure and six mixed cases). Additional somatic mutations affecting breast cancer-related genes found in ACCs included PIK3CA, MTOR, CTNNB1, BRCA1, ERBB4, ERBB3, INPP4B, and FGFR2. Copy number alteration analysis revealed complex patterns of gains and losses similar to those of common forms of TNBCs. Of the mixed cases analysed, identical somatic mutations were found in the acinic and the high-grade non-acinic components in two out of four cases analysed, providing evidence of their clonal relatedness. In conclusion, breast ACCs display the hallmark somatic genetic alterations found in high-grade forms of TNBC, including complex patterns of gene copy number alterations and recurrent TP53 mutations. Furthermore, we provide circumstantial genetic evidence to suggest that ACCs may constitute the substrate for the development of more aggressive forms of triple-negative disease.

Original languageEnglish
Pages (from-to)166-178
Number of pages13
JournalJournal of Pathology
Issue number2
Publication statusPublished - Oct 1 2015


  • breast cancer
  • immunohistochemistry
  • massively parallel sequencing
  • TP53
  • triple-negative

ASJC Scopus subject areas

  • Pathology and Forensic Medicine


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