Synapse - Genetic analysis of microglandular adenosis and acinic cell carcinomas of the breast provides evidence for the existence of a low-grade triple-negative breast neoplasia family

Genetic analysis of microglandular adenosis and acinic cell carcinomas of the breast provides evidence for the existence of a low-grade triple-negative breast neoplasia family Journal Article

Authors:	Geyer, F. C.; Berman, S. H.; Marchiò, C.; Burke, K. A.; Guerini-Rocco, E.; Piscuoglio, S.; Ng, C. K. Y.; Pareja, F.; Wen, H. Y.; Hodi, Z.; Schnitt, S. J.; Rakha, E. A.; Ellis, I. O.; Norton, L.; Weigelt, B.; Reis-Filho, J. S.
Article Title:	Genetic analysis of microglandular adenosis and acinic cell carcinomas of the breast provides evidence for the existence of a low-grade triple-negative breast neoplasia family
Abstract:	Acinic cell carcinoma is an indolent form of invasive breast cancer, whereas microglandular adenosis has been shown to be a neoplastic proliferation. Both entities display a triple-negative phenotype, and may give rise to and display somatic genomic alterations typical of high-grade triple-negative breast cancers. Here we report on a comparison of previously published data on eight carcinoma-associated microglandular adenosis and eight acinic cell carcinomas subjected to targeted massively parallel sequencing targeting all exons of 236 genes recurrently mutated in breast cancer and/or DNA repair-related. Somatic mutations, insertions/deletions, and copy number alterations were detected using state-of-the-art bioinformatic algorithms. All cases were of triple-negative phenotype. A median of 4.5 (1-13) and 4.0 (1-7) non-synonymous somatic mutations per carcinoma-associated microglandular adenosis and acinic cell carcinoma were identified, respectively. TP53 was the sole highly recurrently mutated gene (75% in microglandular adenosis versus 88% in acinic cell carcinomas), and TP53 mutations were consistently coupled with loss of heterozygosity of the wild-type allele. Additional somatic mutations shared by both groups included those in BRCA1, PIK3CA, and INPP4B. Recurrent (n = 2) somatic mutations restricted to microglandular adenosis or acinic cell carcinomas included those affecting PTEN and MED12 or ERBB4, respectively. No significant differences in the repertoire of somatic mutations were detected between microglandular adenosis and acinic cell carcinomas, and between this group of lesions and 77 triple-negative carcinomas from The Cancer Genome Atlas. Microglandular adenosis and acinic cell carcinomas, however, were genetically distinct from estrogen receptor-positive and/or HER2-positive breast cancers from The Cancer Genome Atlas. Our findings support the contention that microglandular adenosis and acinic cell carcinoma are part of the same spectrum of lesions harboring frequent TP53 somatic mutations, and likely represent low-grade forms of triple-negative disease with no/minimal metastatic potential, of which a subset has the potential to progress to high-grade triple-negative breast cancer. © 2017 USCAP, Inc All rights reserved.
Journal Title:	Modern Pathology
Volume:	30
Issue:	1
ISSN:	0893-3952
Publisher:	Nature Research
Date Published:	2017-01-01
Start Page:	69
End Page:	84
Language:	English
DOI:	10.1038/modpathol.2016.161
PROVIDER:	scopus
PMCID:	PMC5221420
PUBMED:	27713419
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-84990188140&doi=10.1038%2fmodpathol.2016.161&partnerID=40&md5=a10a4249a0cdb0df1c3a8ae5876d341c
Notes:	Article -- Export Date: 2 February 2017 -- Source: Scopus