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Abstract
Chromosomal allelic losses have a varying frequency in colorectal cancer. The aim
of this study was to define the target region of allelic loss on chromosome 22q in
human colorectal carcinogenesis.
Fifty-seven pairs of matched normal colonic mucosa and tumor specimens from patients
with colorectal cancer, as well as 15 colon cancer-derived cell lines, were genotyped
using 15 microsatellite markers spanning chromosome 22q. A potential candidate gene
was analyzed by a single-strand conformation polymorphism (SSCP)/direct DNA sequencing
approach.
After excluding 7 tumors with evidence of microsatellite instability, allelic loss
was observed in 11 of the informative tumors (22%), 5 of which exhibited losses in
all informative loci. The remaining 6 tumors showed variable patterns of partial allelic
loss on chromosome 22q, thereby localizing a minimal region of allelic deletion between
markers D22S1171 and D22S928. Physical mapping showed that this interval was 0.57
cM consisting of approximately 425 kilobases. Database searches identified the NBK/BIK
gene, a proapoptotic BCL-2 family member, as a candidate gene in that region. However,
SSCP/sequencing analysis excluded mutations of this gene.
This study provides evidence for the involvement of putative tumor-suppressor gene(s)
on chromosome 22q in human colorectal carcinogenesis. The identification of a 0.5-cM
interval serves as the basis for the isolation of such a gene by positional cloning.