Cloning of breakpoints in and downstream the IGF2 gene that are associated with overexpression of IGF2 transcripts in colorectal tumours.
The human IGF2 gene belongs to a group of imprinted genes clustered on the short arm of chromosome 11, band p15.5. It contains 9 exons and spans over 30 kb. IGF2 mRNA overexpression has been reported in human tumours and in some inherited growth disorders. It was recently demonstrated that IGF2 mRNA overexpression contributes to tumour progression and that loss of parental imprinting as well as altered transcription factors are contributing to this overexpression. We have reported structural alterations in the 3' region of the IGF2 gene in two colorectal tumours that overexpressed the IGF2 transcript by 200- and 800-fold. We cloned by the vectorette-PCR strategy, genomic DNA fragments containing the breakpoints from these tumours. The sequencing of these fragments positioned the breakpoint 2 kb downstream the IGF2 gene in one tumour, and in exon 9 in the second. Both breakpoints occurred in regions containing repetitive elements: a TGGA repeat we have identified downstream the gene, and the (CA)n repetition in exon 9. We hypothesize that a negative regulatory element, located downstream the IGF2 gene, has been deleted following these structural alterations and leads to IGF2 gene overexpression.
Hodzic
D
D
Laboratory of Molecular Oncology, Department of Pathology, University of Liège, Tour de Pathologie B23, Sart Tilman, B-4000 Liège, Belgium.
Frey
B
B
Marechal
D
D
Scarcez
T
T
Grooteclaes
M
M
Winkler
R
R
D002869:Chromosome Aberrations; D025063:Chromosome Disorders; D003001:Cloning, Molecular; D015179:Colorectal Neoplasms / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D015321:Gene Rearrangement; D018392:Genomic Imprinting; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000235:genetics*; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis*; D017422:Sequence Analysis, DNA
D012333:RNA, Messenger; D012334:RNA, Neoplasm; D007335:Insulin-Like Growth Factor II