Cellular/intramuscular myxoma and grade I myxofibrosarcoma are characterized by distinct genetic alterations and specific composition of their extracellular matrix

Cellular myxoma and grade I myxofibrosarcoma are mesenchymal tumours that are characterized by their abundant myxoid extracellular matrix (ECM). Despite their histological overlap, they differ clinically. Diagnosis is therefore difficult though important. We investigated their (cyto) genetics and EC...

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Main Authors:	Willems, Stefan M, Mohseny, Alex B, Balog, Crina, Sewrajsing, Raj, Briaire-de Bruijn, Inge H, Knijnenburg, Jeroen, Cleton-Jansen, Anne-Marie, Sciot, Raf, Fletcher, Christopher D M, Deelder, André M, Szuhai, Karoly, Hensbergen, Paul J, Hogendoorn, Pancras C W
Format:	Online
Language:	English
Published:	John Wiley & Sons, Ltd 2009
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4496143/

id	pubmed-4496143
recordtype	oai_dc
spelling	pubmed-44961432015-07-13 Cellular/intramuscular myxoma and grade I myxofibrosarcoma are characterized by distinct genetic alterations and specific composition of their extracellular matrix Willems, Stefan M Mohseny, Alex B Balog, Crina Sewrajsing, Raj Briaire-de Bruijn, Inge H Knijnenburg, Jeroen Cleton-Jansen, Anne-Marie Sciot, Raf Fletcher, Christopher D M Deelder, André M Szuhai, Karoly Hensbergen, Paul J Hogendoorn, Pancras C W Articles Cellular myxoma and grade I myxofibrosarcoma are mesenchymal tumours that are characterized by their abundant myxoid extracellular matrix (ECM). Despite their histological overlap, they differ clinically. Diagnosis is therefore difficult though important. We investigated their (cyto) genetics and ECM. GNAS1-activating mutations have been described in intramuscular myxoma, and lead to downstream activation of cFos. KRAS and TP53 mutations are commonly involved in sarcomagenesis whereby KRAS subsequently activates c-Fos. A well-documented series of intramuscular myxoma (three typical cases and seven cases of the more challenging cellular variant) and grade I myxofibrosarcoma (n= 10) cases were karyotyped, analyzed for GNAS1, KRAS and TP53 mutations and downstream activation of c-Fos mRNA and protein expression. ECM was studied by liquid chromatography mass spectrometry and expression of proteins identified was validated by immunohistochemistry and qPCR. Grade I myxofibrosarcoma showed variable, non-specific cyto-genetic aberrations in 83,5% of cases (n= 6) whereas karyotypes of intramuscular myxoma were all normal (n= 7). GNAS1-activating mutations were exclusively found in 50% of intramuscular myxoma. Both tumour types showed over-expression of c-Fos mRNA and protein. No mutations in KRAS codon 12/13 or in TP53 were detected. Liquid chromatography mass spectrometry revealed structural proteins (collagen types I, VI, XII, XIV and decorin) in grade I myxofibrosarcoma lacking in intramuscular myxoma. This was confirmed by immunohistochemistry and qPCR. Intramuscular/cellular myxoma and grade I myxofibrosarcoma show different molecular genetic aberrations and different composition of their ECM that probably contribute to their diverse clinical behaviour. GNAS1 mutation analysis can be helpful to distinguish intramuscular myxoma from grade I myxofibrosarcoma in selected cases. John Wiley & Sons, Ltd 2009-07 2009-03-13 /pmc/articles/PMC4496143/ /pubmed/19320777 http://dx.doi.org/10.1111/j.1582-4934.2009.00747.x Text en © 2009 The Authors Journal compilation © 2009 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Willems, Stefan M Mohseny, Alex B Balog, Crina Sewrajsing, Raj Briaire-de Bruijn, Inge H Knijnenburg, Jeroen Cleton-Jansen, Anne-Marie Sciot, Raf Fletcher, Christopher D M Deelder, André M Szuhai, Karoly Hensbergen, Paul J Hogendoorn, Pancras C W
spellingShingle	Willems, Stefan M Mohseny, Alex B Balog, Crina Sewrajsing, Raj Briaire-de Bruijn, Inge H Knijnenburg, Jeroen Cleton-Jansen, Anne-Marie Sciot, Raf Fletcher, Christopher D M Deelder, André M Szuhai, Karoly Hensbergen, Paul J Hogendoorn, Pancras C W Cellular/intramuscular myxoma and grade I myxofibrosarcoma are characterized by distinct genetic alterations and specific composition of their extracellular matrix
author_facet	Willems, Stefan M Mohseny, Alex B Balog, Crina Sewrajsing, Raj Briaire-de Bruijn, Inge H Knijnenburg, Jeroen Cleton-Jansen, Anne-Marie Sciot, Raf Fletcher, Christopher D M Deelder, André M Szuhai, Karoly Hensbergen, Paul J Hogendoorn, Pancras C W
author_sort	Willems, Stefan M
title	Cellular/intramuscular myxoma and grade I myxofibrosarcoma are characterized by distinct genetic alterations and specific composition of their extracellular matrix
title_short	Cellular/intramuscular myxoma and grade I myxofibrosarcoma are characterized by distinct genetic alterations and specific composition of their extracellular matrix
title_full	Cellular/intramuscular myxoma and grade I myxofibrosarcoma are characterized by distinct genetic alterations and specific composition of their extracellular matrix
title_fullStr	Cellular/intramuscular myxoma and grade I myxofibrosarcoma are characterized by distinct genetic alterations and specific composition of their extracellular matrix
title_full_unstemmed	Cellular/intramuscular myxoma and grade I myxofibrosarcoma are characterized by distinct genetic alterations and specific composition of their extracellular matrix
title_sort	cellular/intramuscular myxoma and grade i myxofibrosarcoma are characterized by distinct genetic alterations and specific composition of their extracellular matrix
description	Cellular myxoma and grade I myxofibrosarcoma are mesenchymal tumours that are characterized by their abundant myxoid extracellular matrix (ECM). Despite their histological overlap, they differ clinically. Diagnosis is therefore difficult though important. We investigated their (cyto) genetics and ECM. GNAS1-activating mutations have been described in intramuscular myxoma, and lead to downstream activation of cFos. KRAS and TP53 mutations are commonly involved in sarcomagenesis whereby KRAS subsequently activates c-Fos. A well-documented series of intramuscular myxoma (three typical cases and seven cases of the more challenging cellular variant) and grade I myxofibrosarcoma (n= 10) cases were karyotyped, analyzed for GNAS1, KRAS and TP53 mutations and downstream activation of c-Fos mRNA and protein expression. ECM was studied by liquid chromatography mass spectrometry and expression of proteins identified was validated by immunohistochemistry and qPCR. Grade I myxofibrosarcoma showed variable, non-specific cyto-genetic aberrations in 83,5% of cases (n= 6) whereas karyotypes of intramuscular myxoma were all normal (n= 7). GNAS1-activating mutations were exclusively found in 50% of intramuscular myxoma. Both tumour types showed over-expression of c-Fos mRNA and protein. No mutations in KRAS codon 12/13 or in TP53 were detected. Liquid chromatography mass spectrometry revealed structural proteins (collagen types I, VI, XII, XIV and decorin) in grade I myxofibrosarcoma lacking in intramuscular myxoma. This was confirmed by immunohistochemistry and qPCR. Intramuscular/cellular myxoma and grade I myxofibrosarcoma show different molecular genetic aberrations and different composition of their ECM that probably contribute to their diverse clinical behaviour. GNAS1 mutation analysis can be helpful to distinguish intramuscular myxoma from grade I myxofibrosarcoma in selected cases.
publisher	John Wiley & Sons, Ltd
publishDate	2009
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4496143/
_version_	1613245767543160832

Cellular/intramuscular myxoma and grade I myxofibrosarcoma are characterized by distinct genetic alterations and specific composition of their extracellular matrix

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