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Level of MYC overexpression in pediatric Burkitt's lymphoma is strongly dependent on genomic breakpoint location within the MYC locus
Author(s) -
Wilda Monika,
Busch Kerstin,
Klose Irmgard,
Keller Thomas,
Woessmann Wilhelm,
Kreuder Joachim,
Harbott Jochen,
Borkhardt Arndt
Publication year - 2004
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.20063
Subject(s) - breakpoint , exon , biology , chromosomal translocation , burkitt's lymphoma , gene , microbiology and biotechnology , locus (genetics) , intron , transcription (linguistics) , immunoglobulin heavy chain , promoter , genetics , gene expression , cancer research , cell culture , linguistics , philosophy
Increased transcriptional activity of the MYC gene is a characteristic feature of Burkitt's lymphoma. Aberrant MYC expression is caused by (1) chromosomal translocation to one of the loci carrying an immunoglobulin gene, (2) mutation within the translocated allele, (3) loss of the block to transcription elongation, or (4) promoter shift. To investigate the influence of breakpoint locations within the MYC gene on MYC transcript levels, we determined both the precise genomic MYC/IGH breakpoints and the amount of MYC mRNA in 25 samples of pediatric Burkitt's lymphoma with translocation t(8;14)(q24;q32). Patients with breakpoints that were 5′ from MYC exon 1 had significantly lower expression of MYC than did patients who had a breakpoint within exon 1 or intron 1 ( P < 0.05 and 0.005, respectively). The highest mRNA level of MYC (1,006 copies per 100 copies ABL 1) was detected in patients with loss of the first exon and transcription initiation from a cryptic P3 promoter within the first intron of the MYC gene. In contrast, there was no obvious correlation between breakpoint locations within the IgH locus and the amount of MYC mRNA. © 2004 Wiley‐Liss, Inc.