Fresia Pareja
Assessment of HMGA2 and PLAG1 rearrangements in breast adenomyoepitheliomas
Pareja, Fresia; Geyer, Felipe C.; Brown, David N.; Sebastião, Ana P. Martins; Gularte-Mérida, Rodrigo; Li, Anqi; Edelweiss, Marcia; Da Cruz Paula, Arnaud; Selenica, Pier; Wen, Hannah Y.; Jungbluth, Achim A.; Varga, Zsuzsanna; Palazzo, Juan; Rubin, Brian P.; Ellis, Ian O.; Brogi, Edi; Rakha, Emad A.; Weigelt, Britta; Reis-Filho, Jorge S.
Authors
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
Professor IAN ELLIS IAN.ELLIS@NOTTINGHAM.AC.UK
Professor of Cancer Pathology
Edi Brogi
EMAD RAKHA Emad.Rakha@nottingham.ac.uk
Professor of Breast Cancer Pathology
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.
Citation
Pareja, F., Geyer, F. C., Brown, D. N., Sebastião, A. P. M., Gularte-Mérida, R., Li, A., …Reis-Filho, J. S. (2019). Assessment of HMGA2 and PLAG1 rearrangements in breast adenomyoepitheliomas. npj Breast Cancer, 5, Article 6 (2019). https://doi.org/10.1038/s41523-018-0101-7
Journal Article Type | Article |
---|---|
Acceptance Date | Nov 27, 2018 |
Online Publication Date | Jan 18, 2019 |
Publication Date | Jan 18, 2019 |
Deposit Date | Aug 8, 2019 |
Publicly Available Date | Aug 8, 2019 |
Journal | npj Breast Cancer |
Electronic ISSN | 2374-4677 |
Publisher | Nature Publishing Group |
Peer Reviewed | Peer Reviewed |
Volume | 5 |
Article Number | 6 (2019) |
DOI | https://doi.org/10.1038/s41523-018-0101-7 |
Public URL | https://nottingham-repository.worktribe.com/output/2406433 |
Publisher URL | https://www.nature.com/articles/s41523-018-0101-7 |
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Assessment of HMGA2 and PLAG1 rearrangements in breast adenomyoepitheliomas
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Publisher Licence URL
https://creativecommons.org/licenses/by/4.0/
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