Methylation profiling reveals novel molecular classes of rhabdomyosarcoma

Abstract Rhabdomyosarcomas (RMS) represent a family of aggressive soft tissue sarcomas that present in both children and adults. Pathologic risk stratification for RMS has been based on histologic subtype, with poor outcomes observed in alveolar rhabdomyosarcoma (ARMS) and the adult-type pleomorphic...

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Autores principales:	Michael R. Clay, Anand Patel, Quynh Tran, Dale J. Hedges, Ti-Cheng Chang, Elizabeth Stewart, Greg Charville, Cynthia Cline, Michael A. Dyer, Brent A. Orr
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2a65920f1718448eb362b6a801462e28
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spelling	oai:doaj.org-article:2a65920f1718448eb362b6a801462e282021-11-21T12:17:12ZMethylation profiling reveals novel molecular classes of rhabdomyosarcoma10.1038/s41598-021-01649-w2045-2322https://doaj.org/article/2a65920f1718448eb362b6a801462e282021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-01649-whttps://doaj.org/toc/2045-2322Abstract Rhabdomyosarcomas (RMS) represent a family of aggressive soft tissue sarcomas that present in both children and adults. Pathologic risk stratification for RMS has been based on histologic subtype, with poor outcomes observed in alveolar rhabdomyosarcoma (ARMS) and the adult-type pleomorphic rhabdomyosarcoma (PRMS) compared to embryonal rhabdomyosarcoma (ERMS). Genomic sequencing studies have expanded the spectrum of RMS, with several new molecularly defined entities, including fusion-driven spindle cell/sclerosing rhabdomyosarcoma (SC/SRMS) and MYOD1-mutant SC/SRMS. Comprehensive genomic analysis has previously defined the mutational and copy number spectrum for the more common ERMS and ARMS and revealed corresponding methylation signatures. Comparatively, less is known about epigenetic correlates for the rare SC/SRMS or PRMS histologic subtypes. Herein, we present exome and RNA sequencing, copy number analysis, and methylation profiling of the largest cohort of molecularly characterized RMS samples to date. In addition to ARMS and ERMS, we identify two novel methylation subtypes, one having SC/SRMS histology and defined by MYOD1 p. L122R mutations and the other matching adult-type PRMS. Selected tumors from adolescent patients grouped with the PRMS methylation class, expanding the age range of these rare tumors. Limited follow-up data suggest that pediatric tumors with MYOD1-mutations are associated with an aggressive clinical course.Michael R. ClayAnand PatelQuynh TranDale J. HedgesTi-Cheng ChangElizabeth StewartGreg CharvilleCynthia ClineMichael A. DyerBrent A. OrrNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Michael R. Clay Anand Patel Quynh Tran Dale J. Hedges Ti-Cheng Chang Elizabeth Stewart Greg Charville Cynthia Cline Michael A. Dyer Brent A. Orr Methylation profiling reveals novel molecular classes of rhabdomyosarcoma
description	Abstract Rhabdomyosarcomas (RMS) represent a family of aggressive soft tissue sarcomas that present in both children and adults. Pathologic risk stratification for RMS has been based on histologic subtype, with poor outcomes observed in alveolar rhabdomyosarcoma (ARMS) and the adult-type pleomorphic rhabdomyosarcoma (PRMS) compared to embryonal rhabdomyosarcoma (ERMS). Genomic sequencing studies have expanded the spectrum of RMS, with several new molecularly defined entities, including fusion-driven spindle cell/sclerosing rhabdomyosarcoma (SC/SRMS) and MYOD1-mutant SC/SRMS. Comprehensive genomic analysis has previously defined the mutational and copy number spectrum for the more common ERMS and ARMS and revealed corresponding methylation signatures. Comparatively, less is known about epigenetic correlates for the rare SC/SRMS or PRMS histologic subtypes. Herein, we present exome and RNA sequencing, copy number analysis, and methylation profiling of the largest cohort of molecularly characterized RMS samples to date. In addition to ARMS and ERMS, we identify two novel methylation subtypes, one having SC/SRMS histology and defined by MYOD1 p. L122R mutations and the other matching adult-type PRMS. Selected tumors from adolescent patients grouped with the PRMS methylation class, expanding the age range of these rare tumors. Limited follow-up data suggest that pediatric tumors with MYOD1-mutations are associated with an aggressive clinical course.
format	article
author	Michael R. Clay Anand Patel Quynh Tran Dale J. Hedges Ti-Cheng Chang Elizabeth Stewart Greg Charville Cynthia Cline Michael A. Dyer Brent A. Orr
author_facet	Michael R. Clay Anand Patel Quynh Tran Dale J. Hedges Ti-Cheng Chang Elizabeth Stewart Greg Charville Cynthia Cline Michael A. Dyer Brent A. Orr
author_sort	Michael R. Clay
title	Methylation profiling reveals novel molecular classes of rhabdomyosarcoma
title_short	Methylation profiling reveals novel molecular classes of rhabdomyosarcoma
title_full	Methylation profiling reveals novel molecular classes of rhabdomyosarcoma
title_fullStr	Methylation profiling reveals novel molecular classes of rhabdomyosarcoma
title_full_unstemmed	Methylation profiling reveals novel molecular classes of rhabdomyosarcoma
title_sort	methylation profiling reveals novel molecular classes of rhabdomyosarcoma
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/2a65920f1718448eb362b6a801462e28
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Methylation profiling reveals novel molecular classes of rhabdomyosarcoma

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