Journal
ONCOGENE
Volume 27, Issue 3, Pages 318-322Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.onc.1210650
Keywords
DNA damage; 53BP1; lymphoma; genetic abnormalities; high-density single nucleotide polymorphism array
Funding
- NCI NIH HHS [P01 CA092625, K08 CA122833-01A1, P01 CA92625, K08 CA122833] Funding Source: Medline
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p53-Binding protein 1 (53BP1) encodes a critical checkpoint protein that localizes to sites of DNA double-strand breaks (DSBs) and participates in DSB repair. Mice that are 53bp1 deficient or hemizygous have an increased incidence of lymphoid malignancies. However, 53BP1 abnormalities in primary human tumors have not been described. By combining high-density single nucleotide polymorphism (HD SNP) array data and gene expression profiles, we found 9 of 63 newly diagnosed human diffuse large B-cell lymphomas (DLBCLs) with single copy loss of the chromosome 15q15 region including the 53BP1 locus; these nine tumors also had significantly lower levels of 53BP1 transcripts. 53BP1 single copy loss found with the HD SNP array platform was subsequently confirmed by fluorescence in situ hybridization. These studies highlight the role of 53BP1 copy loss in primary human DLBCLs and the value of integrative analyses in detecting this genetic lesion in human tumors.
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