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Whole-Exome and RNA-Sequencing Analyses of Acinic Cell Carcinomas of the Breast

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


Francisco Beca

Simon S.K. Lee

Fresia Pareja

Arnaud da Cruz Paula

Pier Selenica

Lorenzo Ferrando

Rodrigo Gularte‐Merida

Hannah Y Wen

Hong Zhang

Elena Guerini‐Rocco

Emad A. Rakha

Britta Weigelt

Jorge S. Reis‐Filho


Acinic cell carcinoma of the breast (ACC) is a rare histologic 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, seeking to define whether they would harbor a pathognomonic genetic alteration.

Methods and Results
Tumor and normal DNA and RNA samples from three breast ACCs were subjected to whole‐exome sequencing. Somatic mutations, copy number alterations, mutational signatures and fusion genes were determined using 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 (HR) DNA repair‐related genes were found in two cases, and an MLH1 pathogenic germline variant was detected 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 analyzed.

No pathognomonic genetic alterations were detected in the ACCs analyzed. These tumors have somatic genetic alterations similar to those of common forms of TNBC and may display HR deficiency or microsatellite instability. These findings provide further insights as to why ACCs which are usually clinically indolent may evolve into or in parallel with high‐grade TNBC.

Journal Article Type Article
Publication Date Jul 30, 2019
Journal Histopathology
Print ISSN 0309-0167
Electronic ISSN 1365-2559
Publisher Wiley
Peer Reviewed Peer Reviewed
Institution Citation Beca, F., Lee, S. S., Pareja, F., da Cruz Paula, A., Selenica, P., Ferrando, L., …Reis‐Filho, J. S. (2019). Whole-Exome and RNA-Sequencing Analyses of Acinic Cell Carcinomas of the Breast. Histopathology, doi:10.1111/his.13962
Keywords Pathology and Forensic Medicine; Histology; General Medicine
Publisher URL


This file is under embargo until Jul 30, 2020 due to copyright restrictions.

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