EZH2 codon 641 mutations are common in BCL2-rearranged germinal center B cell lymphomas.

Mutations at codon 641 of EZH2 are recurrent in germinal center B cell lymphomas, and the most common variants lead to altered EZH2 enzymatic activity and enhanced tri-methylation of histone H3 at lysine 27, a repressive chromatin modification. As an initial step toward screening patients for cancer...

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Autores principales:	Russell J H Ryan, Mai Nitta, Darrell Borger, Lawrence R Zukerberg, Judith A Ferry, Nancy Lee Harris, A John Iafrate, Bradley E Bernstein, Aliyah R Sohani, Long Phi Le
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/bf516049533c48d780c32bc7b0f7af86
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spelling	oai:doaj.org-article:bf516049533c48d780c32bc7b0f7af862021-11-18T07:32:19ZEZH2 codon 641 mutations are common in BCL2-rearranged germinal center B cell lymphomas.1932-620310.1371/journal.pone.0028585https://doaj.org/article/bf516049533c48d780c32bc7b0f7af862011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22194861/?tool=EBIhttps://doaj.org/toc/1932-6203Mutations at codon 641 of EZH2 are recurrent in germinal center B cell lymphomas, and the most common variants lead to altered EZH2 enzymatic activity and enhanced tri-methylation of histone H3 at lysine 27, a repressive chromatin modification. As an initial step toward screening patients for cancer genotype-directed therapy, we developed a screening assay for EZH2 codon 641 mutations amenable for testing formalin-fixed clinical specimens, based on the sensitive SNaPshot single nucleotide extension technology. We detected EZH2 mutations in 12/55 (22%) follicular lymphomas (FL), 5/35 (14%) diffuse large B cell lymphomas with a germinal center immunophenotype (GCB-DLBCL), and 2/11 (18%) high grade B cell lymphomas with concurrent rearrangements of BCL2 and MYC. No EZH2 mutations were detected in cases of Burkitt lymphoma (0/23). EZH2 mutations were frequently associated with the presence of BCL2 rearrangement (BCL2-R) in both the FL (28% of BCL-R cases versus 0% of BCL2-WT cases, p<0.05) and GCB-DLBCL groups (33% of BCL2-R cases versus 4% of BCL2-WT cases, p<0.04), and across all lymphoma types excluding BL (27% of BCL2-R cases versus 3% of BCL2-WT cases, p<0.003). We confirmed gain-of-function activity for all previously reported EZH2 codon 641 mutation variants. Our findings suggest that EZH2 mutations constitute an additional genetic "hit" in many BCL2-rearranged germinal center B cell lymphomas. Our work may be helpful in the selection of lymphoma patients for future trials of pharmacologic agents targeting EZH2 and EZH2-regulated pathways.Russell J H RyanMai NittaDarrell BorgerLawrence R ZukerbergJudith A FerryNancy Lee HarrisA John IafrateBradley E BernsteinAliyah R SohaniLong Phi LePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 12, p e28585 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Russell J H Ryan Mai Nitta Darrell Borger Lawrence R Zukerberg Judith A Ferry Nancy Lee Harris A John Iafrate Bradley E Bernstein Aliyah R Sohani Long Phi Le EZH2 codon 641 mutations are common in BCL2-rearranged germinal center B cell lymphomas.
description	Mutations at codon 641 of EZH2 are recurrent in germinal center B cell lymphomas, and the most common variants lead to altered EZH2 enzymatic activity and enhanced tri-methylation of histone H3 at lysine 27, a repressive chromatin modification. As an initial step toward screening patients for cancer genotype-directed therapy, we developed a screening assay for EZH2 codon 641 mutations amenable for testing formalin-fixed clinical specimens, based on the sensitive SNaPshot single nucleotide extension technology. We detected EZH2 mutations in 12/55 (22%) follicular lymphomas (FL), 5/35 (14%) diffuse large B cell lymphomas with a germinal center immunophenotype (GCB-DLBCL), and 2/11 (18%) high grade B cell lymphomas with concurrent rearrangements of BCL2 and MYC. No EZH2 mutations were detected in cases of Burkitt lymphoma (0/23). EZH2 mutations were frequently associated with the presence of BCL2 rearrangement (BCL2-R) in both the FL (28% of BCL-R cases versus 0% of BCL2-WT cases, p<0.05) and GCB-DLBCL groups (33% of BCL2-R cases versus 4% of BCL2-WT cases, p<0.04), and across all lymphoma types excluding BL (27% of BCL2-R cases versus 3% of BCL2-WT cases, p<0.003). We confirmed gain-of-function activity for all previously reported EZH2 codon 641 mutation variants. Our findings suggest that EZH2 mutations constitute an additional genetic "hit" in many BCL2-rearranged germinal center B cell lymphomas. Our work may be helpful in the selection of lymphoma patients for future trials of pharmacologic agents targeting EZH2 and EZH2-regulated pathways.
format	article
author	Russell J H Ryan Mai Nitta Darrell Borger Lawrence R Zukerberg Judith A Ferry Nancy Lee Harris A John Iafrate Bradley E Bernstein Aliyah R Sohani Long Phi Le
author_facet	Russell J H Ryan Mai Nitta Darrell Borger Lawrence R Zukerberg Judith A Ferry Nancy Lee Harris A John Iafrate Bradley E Bernstein Aliyah R Sohani Long Phi Le
author_sort	Russell J H Ryan
title	EZH2 codon 641 mutations are common in BCL2-rearranged germinal center B cell lymphomas.
title_short	EZH2 codon 641 mutations are common in BCL2-rearranged germinal center B cell lymphomas.
title_full	EZH2 codon 641 mutations are common in BCL2-rearranged germinal center B cell lymphomas.
title_fullStr	EZH2 codon 641 mutations are common in BCL2-rearranged germinal center B cell lymphomas.
title_full_unstemmed	EZH2 codon 641 mutations are common in BCL2-rearranged germinal center B cell lymphomas.
title_sort	ezh2 codon 641 mutations are common in bcl2-rearranged germinal center b cell lymphomas.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/bf516049533c48d780c32bc7b0f7af86
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EZH2 codon 641 mutations are common in BCL2-rearranged germinal center B cell lymphomas.

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