Mountain View
biomedical and healthCAre Data Discovery Index Ecosystem
help Advanced Search
Title: Whole Exome Sequencing of Diffuse Large B-Cell Lymphoma      
Identifier:
phs000450.v2.p1
description:
We performed massively parallel whole exome sequencing of 55 primary tumor samples from patients with diffuse large B cell lymphoma (DLBCL) and matched normal tissue. We identified recurrent mutations in genes that are well known to be functionally relevant in DLBCL, as well as in genes for which a functional role in DLBCL has not been previously suspected. Significantly mutated genes include MYD88, CARD11, EZH2, CREBBP, as well as MEF2B, MLL2, BTG1, GNA13, ACTB, P2RY8, PCLO and TNFRSF14. Analysis of somatic mutations in patients with DLBCL also revealed that BCL2 mutations commonly occur in patients with BCL2/IgH rearrangements as a result of somatic hypermutation normally occurring at the IgH locus. The BCL2 point mutations are primarily synonymous, likely caused by AID-mediated somatic hypermutation, and those non-synonymous mutations that are observed tend to be found outside of the functionally important BH domains of the protein, suggesting that strong negative selection against BCL2 loss-of-function mutations is at play. We further identified genes with mutations that are likely to be functionally relevant despite being mutated at a low rate. These genes include KRAS, BRAF and NOTCH1 as likely drivers of DLBCL pathogenesis in some patients. Our data provide an unbiased view of the landscape of mutations in DLBCL. These data may point towards new targets for the treatment of DLBCL.
accesstypes:
download
enclave
landingpage: http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000450.v2.p1
authentication: simpleLogin
none
authorization:
none
duaIndividual
name:
Diffuse Large B-Cell Lymphoma
affiliations:
Broad Institute, Cambridge MA, Dana Farber Cancer Institute, Boston MA
name:
Todd Golub
roles:
Principal Investigator
affiliations:
Broad Institute, Cambridge MA, Dana Farber Cancer Institute, Boston MA
name:
Jens Lohr
roles:
Principal Investigator
affiliations:
Mayo Clinic, Rochester MN
name:
James Cerhan
roles:
Principal Investigator
affiliations:
Slim Initiative for Genomic Medicine
name:
Carlos Slim Health Institute, Mexico City, Mexico
roles:
Funding Source
performedBy:
TitleNameInstitute Principal InvestigatorTodd GolubBroad Institute, Cambridge MA, Dana Farber Cancer Institute, Boston MA Principal InvestigatorJens LohrBroad Institute, Cambridge MA, Dana Farber Cancer Institute, Boston MA Principal InvestigatorJames CerhanMayo Clinic, Rochester MN Funding SourceCarlos Slim Health Institute, Mexico City, MexicoSlim Initiative for Genomic Medicine
downloadURL: https://dbgap.ncbi.nlm.nih.gov/aa/wga.cgi?page=DUC&view_pdf&stacc=phs000450.v2.p1
Identifier:
phs000450.v2.p1_policy
name:
Data Use Certificate
Identifier:
1
name:
General Research Use (NPU, MDS)
Identifier:
2
name:
Disease-Specific (Blood and Lymph Disorders, MDS)
alternateIdentifiers:
yes
dateReleased:
04-09-2014
version:
phs000450.v2.p1
dateModified:
04-09-2014
abbreviation:
NCI
name:
NCI
ID:
0
name:
dbGaP