Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1999-9-21
pubmed:databankReference
http://linkedlifedata.com/resource/pubmed/xref/GENBANK/AF097594, http://linkedlifedata.com/resource/pubmed/xref/GENBANK/AF097595, http://linkedlifedata.com/resource/pubmed/xref/GENBANK/AF097596, http://linkedlifedata.com/resource/pubmed/xref/GENBANK/AF097597, http://linkedlifedata.com/resource/pubmed/xref/GENBANK/AF097598, http://linkedlifedata.com/resource/pubmed/xref/GENBANK/AF097599, http://linkedlifedata.com/resource/pubmed/xref/GENBANK/AF097600, http://linkedlifedata.com/resource/pubmed/xref/GENBANK/AF097606, http://linkedlifedata.com/resource/pubmed/xref/GENBANK/AF097608, http://linkedlifedata.com/resource/pubmed/xref/GENBANK/AF097609, http://linkedlifedata.com/resource/pubmed/xref/GENBANK/AF097612, http://linkedlifedata.com/resource/pubmed/xref/GENBANK/AF097613, http://linkedlifedata.com/resource/pubmed/xref/GENBANK/AF097614, http://linkedlifedata.com/resource/pubmed/xref/GENBANK/AF097615, http://linkedlifedata.com/resource/pubmed/xref/GENBANK/AF097616, http://linkedlifedata.com/resource/pubmed/xref/GENBANK/AF097617, http://linkedlifedata.com/resource/pubmed/xref/GENBANK/AF097618, http://linkedlifedata.com/resource/pubmed/xref/GENBANK/AF097619, http://linkedlifedata.com/resource/pubmed/xref/GENBANK/AF097620, http://linkedlifedata.com/resource/pubmed/xref/GENBANK/AF097621, http://linkedlifedata.com/resource/pubmed/xref/GENBANK/AF097622, http://linkedlifedata.com/resource/pubmed/xref/GENBANK/AF097623
pubmed:abstractText
Three established Burkitt's lymphoma (BL) cell lines (Daudi, Raji and DG-75) and three B-non-Hodgkin's lymphoma (B-NHL) of other types (Pfeiffer, Farage and Toledo) were analyzed with respect to the presence of somatic point mutations in their rearranged immunoglobulin Vkappa genes. Two of the Vkappa sequences of BL and two of those of the B-NHL were heavily mutated (up to 11%), when compared with their closest germline variable region counterparts ("clonal mutations"). Only one of the six cell lines contained an unmutated germline Vkappa sequence. The clonal mutations have features characteristic of the mutation machinery operating in the course of the T-dependent immune response, such as a preference of mutations in purine bases, more transitions than transversions and targeting to CDR and to known "hotspot" motifs. Sequence variations among different Vkappa PCR clones isolated from each of the cell lines ("intraclonal mutations") showed that the Vkappa of Toledo exhibited about 5-fold higher mutation frequency (MF) than the background level of Taq polymerase error (approximately 0.12% mut/bp). Similarly, the MF of Vkappa of two of the BL cell lines was 3-4-fold higher than the Taq polymerase misincorporation rate. In contrast, the mutation frequencies of the Vkappa of DG-75, Farage and Pfeiffer did not significantly exceed the level of Taq polymerase error. Our combined results show that 5 out of the 6 B-cell lines studied originated from B-cells that have already somatically mutated in vivo their rearranged Vkappa genes. Moreover, two of the Burkitt's and one of the B-NHL cell lines exhibit intraclonal variation indicating that the process of somatic hypermutation continued following the neoplastic event, either in vivo or in culture. These results are in accord with the presumed origin of the majority of the BL and some types of the B-NHL, from centrocytes or centroblasts of the germinal centers in which the process of somatic hypermutation is taking place.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0902-4441
pubmed:author
pubmed:issnType
Print
pubmed:volume
63
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
180-91
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Somatic mutations and intraclonal variations in the rearranged Vkappa genes of B-non-Hodgkin's lymphoma cell lines.
pubmed:affiliation
Hubert Humphrey Center for Experimental Medicine and Cancer Research, Hadassah University Hospital, The Hebrew University-Hadassah Medical School, Jerusalem, Israel.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't