Hypermutation of multiple proto-oncogenes in B-cell diffuse large-cell lymphomas

Laura Pasqualucci, Peter Neumeister, Tina Goossens, Gouri Nanjangud, R. S. K. Chaganti, Ralf Küppers and Riccardo Dalla-Favera ()
Additional contact information
Laura Pasqualucci: Columbia University
Peter Neumeister: Columbia University
Tina Goossens: Institute for Genetics, University of Cologne
Gouri Nanjangud: Memorial Sloan-Kettering Cancer Center
R. S. K. Chaganti: Memorial Sloan-Kettering Cancer Center
Ralf Küppers: Columbia University
Riccardo Dalla-Favera: Columbia University

Nature, 2001, vol. 412, issue 6844, 341-346

Abstract: Abstract Genomic instability promotes tumorigenesis and can occur through various mechanisms, including defective segregation of chromosomes or inactivation of DNA mismatch repair1. Although B-cell lymphomas are associated with chromosomal translocations that deregulate oncogene expression2, a mechanism for genome-wide instability during lymphomagenesis has not been described. During B-cell development, the immunoglobulin variable (V) region genes are subject to somatic hypermutation in germinal-centre B cells3. Here we report that an aberrant hypermutation activity targets multiple loci, including the proto-oncogenes PIM1, MYC, RhoH/TTF (ARHH) and PAX5, in more than 50% of diffuse large-cell lymphomas (DLCLs), which are tumours derived from germinal centres. Mutations are distributed in the 5′ untranslated or coding sequences, are independent of chromosomal translocations, and share features typical of V-region-associated somatic hypermutation. In contrast to mutations in V regions, however, these mutations are not detectable in normal germinal-centre B cells or in other germinal-centre-derived lymphomas, suggesting a DLCL-associated malfunction of somatic hypermutation. Intriguingly, the four hypermutable genes are susceptible to chromosomal translocations in the same region, consistent with a role for hypermutation in generating translocations by DNA double-strand breaks4,5,6. By mutating multiple genes, and possibly by favouring chromosomal translocations, aberrant hypermutation may represent the major contributor to lymphomagenesis.

Date: 2001
References: Add references at CitEc
Citations: View citations in EconPapers (3)

Downloads: (external link)
https://www.nature.com/articles/35085588 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:412:y:2001:i:6844:d:10.1038_35085588

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/35085588

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().