Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2003-8-21
pubmed:abstractText
The pathogenesis of AIDS-related non-Hodgkin lymphomas (AIDS-NHLs) is associated with chromosomal translocations that deregulate the expression of various oncogenes. Recently, a novel mechanism of genetic lesion, termed aberrant hypermutation, has been identified in diffuse large B-cell lymphoma (DLBCL) of immunocompetent hosts. In these tumors, the somatic hypermutation (SHM) process that normally targets immunoglobulin V (IgV) genes in B cells appears to misfire and causes mutations in the 5' sequences of multiple proto-oncogenes, including PIM-1, PAX-5, RhoH/TTF, and c-MYC. To investigate whether aberrant hypermutation occurs also in AIDS-NHL, we studied the mutation profile of these 4 genes in various histologic subtypes. Mutations in 1 gene or more were detected in 19 of 39 (48.7%) AIDS-NHL cases (10 of 18 AIDS-diffuse large B-cell lymphoma; 4 of 11 AIDS-Burkitt lymphoma; 4 of 6 AIDS-primary effusion lymphoma; 1 of 4 AIDS-primary central nervous system lymphoma), with 9 of 39 (23.1%) cases carrying mutations in 2 or more genes. Overall, PIM-1 was mutated in 5 of 39 (12.8%), PAX-5 in 8 of 39 (20.5%), RhoH/TTF in 9 of 39 (23.1%), and c-MYC in 7 of 27 (25.9%) AIDS-NHL cases. Mutations were represented mainly by single base pair substitutions (n = 63) with rare deletions/insertions (n = 5) and displayed features typical of the IgV-associated SHM process. In addition, a number of mutations in PIM-1 and c-MYC were found to affect coding exons, leading to amino acid substitutions with likely functional consequences. Analysis of intraclonal heterogeneity documented that the aberrant hypermutation activity may be ongoing in at least some cases. These data indicate that aberrant hypermutation is associated with various subtypes of AIDS-NHL and may represent a major contributor to their pathogenesis.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/B-Cell-Specific Activator Protein, http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin Variable Region, http://linkedlifedata.com/resource/pubmed/chemical/PAX5 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/PIM1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-bcl-6, http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-myc, http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-pim-1, http://linkedlifedata.com/resource/pubmed/chemical/RhoH protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors, http://linkedlifedata.com/resource/pubmed/chemical/rho GTP-Binding Proteins
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0006-4971
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
102
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1833-41
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:12714522-Amino Acid Sequence, pubmed-meshheading:12714522-B-Cell-Specific Activator Protein, pubmed-meshheading:12714522-B-Lymphocytes, pubmed-meshheading:12714522-DNA Mutational Analysis, pubmed-meshheading:12714522-DNA-Binding Proteins, pubmed-meshheading:12714522-Gene Expression Regulation, Neoplastic, pubmed-meshheading:12714522-Humans, pubmed-meshheading:12714522-Immunoglobulin Variable Region, pubmed-meshheading:12714522-Lymphoma, AIDS-Related, pubmed-meshheading:12714522-Lymphoma, Non-Hodgkin, pubmed-meshheading:12714522-Molecular Sequence Data, pubmed-meshheading:12714522-Mutation, Missense, pubmed-meshheading:12714522-Protein-Serine-Threonine Kinases, pubmed-meshheading:12714522-Proto-Oncogene Proteins, pubmed-meshheading:12714522-Proto-Oncogene Proteins c-bcl-6, pubmed-meshheading:12714522-Proto-Oncogene Proteins c-myc, pubmed-meshheading:12714522-Proto-Oncogene Proteins c-pim-1, pubmed-meshheading:12714522-Somatic Hypermutation, Immunoglobulin, pubmed-meshheading:12714522-Transcription Factors, pubmed-meshheading:12714522-rho GTP-Binding Proteins
pubmed:year
2003
pubmed:articleTitle
Aberrant somatic hypermutation in multiple subtypes of AIDS-associated non-Hodgkin lymphoma.
pubmed:affiliation
Institute for Cancer Genetics, Columbia University, Russ Berrie Science Pavilion, 1150 St Nicholas Ave, Rm 303B, New York, NY 10032, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't