Synapse - Uterine adenosarcomas are mesenchymal neoplasms

Uterine adenosarcomas are mesenchymal neoplasms Journal Article

Authors:	Piscuoglio, S.; Burke, K. A.; Ng, C. K. Y.; Papanastasiou, A. D.; Geyer, F. C.; Macedo, G. S.; Martelotto, L. G.; De Bruijn, I.; De Filippo, M. R.; Schultheis, A. M.; Ioris, R. A.; Levine, D. A.; Soslow, R. A.; Rubin, B. P.; Reis-Filho, J. S.; Weigelt, B.
Article Title:	Uterine adenosarcomas are mesenchymal neoplasms
Abstract:	Uterine adenosarcomas (UAs) are biphasic lesions composed of a malignant mesenchymal (ie stromal) component and an epithelial component. UAs are generally low-grade and have a favourable prognosis, but may display sarcomatous overgrowth (SO), which is associated with a worse outcome. We hypothesized that, akin to breast fibroepithelial lesions, UAs are mesenchymal neoplasms in which clonal somatic genetic alterations are restricted to the mesenchymal component. To characterize the somatic genetic alterations in UAs and to test this hypothesis, we subjected 20 UAs to a combination of whole-exome (n = 6), targeted capture (n = 13) massively parallel sequencing (MPS) and/or RNA sequencing (n = 6). Only three genes, FGFR2, KMT2C and DICER1, were recurrently mutated, all in 2/19 cases; however, 26% (5/19) and 21% (4/19) of UAs harboured MDM2/CDK4/HMGA2 and TERT gene amplification, respectively, and two cases harboured fusion genes involving NCOA family members. Using a combination of laser-capture microdissection and in situ techniques, we demonstrated that the somatic genetic alterations detected by MPS were restricted to the mesenchymal component. Furthermore, mitochondrial DNA sequencing of microdissected samples revealed that epithelial and mesenchymal components of UAs were clonally unrelated. In conclusion, here we provide evidence that UAs are genetically heterogeneous lesions and mesenchymal neoplasms. © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Keywords:	fish; massively parallel sequencing; uterine adenosarcoma; rna sequencing
Journal Title:	Journal of Pathology
Volume:	238
Issue:	3
ISSN:	0022-3417
Publisher:	Wiley Blackwell
Date Published:	2016-02-01
Start Page:	381
End Page:	388
Language:	English
DOI:	10.1002/path.4675
PROVIDER:	scopus
PUBMED:	26592504
PMCID:	PMC4986517
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-84956763981&partnerID=40&md5=72738b806503f7b204f47e59304c0296
Notes:	Article -- Export Date: 3 March 2016 -- Source: Scopus