Assessment of HMGA2 and PLAG1 rearrangements in breast adenomyoepitheliomas View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-12

AUTHORS

Fresia Pareja, Felipe C. Geyer, David N. Brown, Ana P. Martins Sebastião, Rodrigo Gularte-Mérida, Anqi Li, Marcia Edelweiss, Arnaud Da Cruz Paula, Pier Selenica, Hannah Y. Wen, Achim A. Jungbluth, Zsuzsanna Varga, Juan Palazzo, Brian P. Rubin, Ian O. Ellis, Edi Brogi, Emad A. Rakha, Britta Weigelt, Jorge S. Reis-Filho

ABSTRACT

Breast adenomyoepitheliomas (AMEs) are rare epithelial-myoepithelial neoplasms that may occasionally produce myxochondroid matrix, akin to pleomorphic adenomas (PAs). Regardless of their anatomic location, PAs often harbor rearrangements involving HMGA2 or PLAG1. We have recently shown that the repertoire of somatic genetic alterations of AMEs varies according to their estrogen receptor (ER) status; whilst the majority of ER-positive AMEs display mutually exclusive PIK3CA or AKT1 hotspot mutations, up to 60% of ER-negative AMEs harbor concurrent HRAS Q61 hotspot mutations and mutations affecting either PIK3CA or PIK3R1. Here, we hypothesized that a subset of AMEs lacking these somatic genetic alterations could be underpinned by oncogenic fusion genes, in particular those involving HMGA2 or PLAG1. Therefore, we subjected 13 AMEs to RNA-sequencing for fusion discovery (n = 5) and/or fluorescence in situ hybridization (FISH) analysis for HMGA2 and PLAG1 rearrangements (n = 13). RNA-sequencing revealed an HMGA2-WIF1 fusion gene in an ER-positive AME lacking HRAS, PIK3CA and AKT1 somatic mutations. This fusion gene, which has been previously described in salivary gland PAs, results in a chimeric transcript composed of exons 1-5 of HMGA2 and exons 3-10 of WIF1. No additional in-frame fusion genes or HMGA2 or PLAG1 rearrangements were identified in the remaining AMEs analyzed. Our results demonstrate that a subset of AMEs lacking mutations affecting HRAS and PI3K pathway-related genes may harbor HMGA2-WIF1 fusion genes, suggesting that a subset of breast AMEs may be genetically related to PAs or that a subset of AMEs may originate in the context of a PA. More... »

PAGES

6

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41523-018-0101-7

DOI

http://dx.doi.org/10.1038/s41523-018-0101-7

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1111506235

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30675516


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