Synapse - Phyllodes tumors with and without fibroadenoma-like areas display distinct genomic features and may evolve through distinct pathways

Phyllodes tumors with and without fibroadenoma-like areas display distinct genomic features and may evolve through distinct pathways Journal Article

Authors:	Pareja, F.; Geyer, F. C.; Kumar, R.; Selenica, P.; Piscuoglio, S.; Ng, C. K. Y.; Burke, K. A.; Edelweiss, M.; Murray, M. P.; Brogi, E.; Weigelt, B.; Reis-Filho, J. S.
Article Title:	Phyllodes tumors with and without fibroadenoma-like areas display distinct genomic features and may evolve through distinct pathways
Abstract:	Breast fibroepithelial lesions (fibroadenomas and phyllodes tumors) are underpinned by recurrent MED12 exon 2 mutations, which are more common in fibroadenomas and benign phyllodes tumors. TERT promoter hotspot mutations have been documented in phyllodes tumors, and found to be more frequent in borderline and malignant lesions. Several lines of evidence suggest that a subset of phyllodes tumors might arise from fibroadenomas. Here we sought to investigate the genetic differences between phyllodes tumors with fibroadenoma-like areas vs. those without. We retrieved data for 16 borderline/ malignant phyllodes tumors, including seven phyllodes tumors with fibroadenoma-like areas and nine phyllodes tumors without fibroadenoma-like areas, which had been previously subjected to targeted capture massively parallel sequencing. Whilst MED12 exon 2 mutations were significantly more frequent in tumors with fibroadenoma-like areas (71 vs. 11%), an enrichment in genetic alterations targeting bona fide cancer genes was found in those without fibroadenoma-like areas, in particular in EGFR mutations and amplifications (78 vs. 14%). No significant difference in the frequency of TERT genetic alterations was observed (71% in cases with fibroadenoma-like areas vs 56% in those without fibroadenoma-like areas). Our data suggest that the development of phyllodes tumors might follow two different evolutionary pathways: a MED12-mutant pathway that involves the progression from a fibroadenoma to a malignant phyllodes tumor; and a MED12-wild-type pathway, where malignant phyllodes tumors arise de novo through the acquisition of genetic alterations targeting cancer genes. Additional studies are warranted to confirm our observations and define whether the outcome differs between both pathways.
Keywords:	targets; progression; breast-cancer; inhibitors; growth-factor receptor; discovery; somatic mutations; dna-sequencing data; frequent med12 mutations; fibroepithelial tumors
Journal Title:	npj Breast Cancer
Volume:	3
ISSN:	2374-4677
Publisher:	Nature Publishing Group
Date Published:	2017-10-12
Start Page:	40
Language:	English
ACCESSION:	WOS:000414569400001
DOI:	10.1038/s41523-017-0042-6
PROVIDER:	wos
PMCID:	PMC5638820
PUBMED:	29043292
Notes:	Article -- Source: Wos