Whole?exome sequencing 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.

Abstract

Aims
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.

Conclusions
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.

Citation

Beca, F., Lee, S. S., Pareja, F., da Cruz Paula, A., Selenica, P., Ferrando, L., …Reis‐Filho, J. S. (2019). Whole‐exome sequencing and RNA sequencing analyses of acinic cell carcinomas of the breast. Histopathology, 75(6), 931-937. https://doi.org/10.1111/his.13962

• Journal Article Type: Article
• Acceptance Date: Jul 30, 2019
• Online Publication Date: Jul 30, 2019
• Publication Date: Dec 31, 2019
• Deposit Date: Aug 13, 2019
• Publicly Available Date: Jul 31, 2020
• Journal: Histopathology
• Print ISSN: 0309-0167
• Electronic ISSN: 1365-2559
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 75
• Issue: 6
• Pages: 931-937
• DOI: https://doi.org/10.1111/his.13962
• Keywords: Pathology and Forensic Medicine; Histology; General Medicine
• Public URL: https://nottingham-repository.worktribe.com/output/2422963
• Publisher URL: https://onlinelibrary.wiley.com/doi/abs/10.1111/his.13962