MUC1 is activated in a B-cell lymphoma by the t(1;14)(q21;q32) translocation and is rearranged and amplified in B-cell lymphoma subsets Journal Article

Authors: Dyomin, V. G.; Palanisamy, N.; Lloyd, K. O.; Dyomina, K.; Jhanwar, S. C.; Houldsworth, J.; Chaganti, R. S. K.
Article Title: MUC1 is activated in a B-cell lymphoma by the t(1;14)(q21;q32) translocation and is rearranged and amplified in B-cell lymphoma subsets
Abstract: The band 1q21 is among the most common sites affected by chromosomal translocations in lymphoid, myeloid, epithelial, and sarcomatous lesions. In non-Hodgkin's lymphoma (NHL), translocations and duplications affecting this chromosomal site are frequently, but not exclusively, seen in association with primary abnormalities such as the t(14; 18)(q32;q21) and t(8;14)(q24;q32) translocations, suggesting a role for 1q21 rearrangements in tumor progression. We report here the characterization and cloning of breakpoints in a case of extranodal ascitic B-cell lymphoma with a t(1;14)(q21; q32) translocation. The breakpoints on the der(l) and der(14) chromosomes were mapped by fluorescence in situ hybridization and Southern blot analysis and cloned using an IGHG (Cγ) probe. The translocation linked the IGHG4 switch (Sγ4) sequences of the productively rearranged allele to chromosome 1 sequences downstream of MUC1, leaving the MUC1 transcriptional unit intact. MUC1 was markedly overexpressed in the tumor at the mRNA and protein levels relative to lymphoma cell lines lacking a 1q21 rearrangement. Presumably, MUC1 transcription is aberrantly regulated by the IGHA (Cα) 3' enhancer element retained on the same chromosome. Screening of a panel of B- cell lymphomas by Southern blot analysis identified a subset with a 3' MUC1 breakpoint and another with low-level amplification of MUC1. MUC-1 mucin has previously beer shown to be frequently overexpressed in human epithelial cancers and to be associated with tumor progression and poor clinical outcome. Thus, MUC1 activation by chromosomal translocation, rearrangement, and amplification, identified here for the first time in NHL, is consistent with its suggested role in tumorigenesis. (C) 2000 by The American Society of Hematology.
Keywords: controlled study; unclassified drug; human cell; nonhuman; animal cell; mouse; allele; gene overexpression; gene product; carcinogenesis; molecular cloning; b cell lymphoma; gene expression regulation, neoplastic; lymphoma, b-cell; gene rearrangement; molecular sequence data; base sequence; translocation, genetic; mucin 1; chromosomes, human, pair 1; chromosome 1q; genetic markers; chromosome mapping; mucins; chromosomes, human, pair 14; humans; human; priority journal; article; b-lymphocyte subsets; chromosome translocation 1; dna probe
Journal Title: Blood
Volume: 95
Issue: 8
ISSN: 0006-4971
Publisher: American Society of Hematology  
Date Published: 2000-04-15
Start Page: 2666
End Page: 2671
Language: English
PUBMED: 10753849
PROVIDER: scopus
Notes: Export Date: 18 November 2015 -- Source: Scopus