Mapping of a target region of allelic loss to a 0.5-cM interval on chromosome 22q13 in human colorectal cancer.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Castells
A
A
Molecular Neurogenetics Unit, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA.
Ino
Y
Y
Louis
D N
DN
Ramesh
V
V
Gusella
J F
JF
Rustgi
A K
AK
D000483:Alleles; D017209:Apoptosis / Q000235:genetics; D002460:Cell Line; D002874:Chromosome Mapping; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics*; D003106:Colon / Q000502:physiology; D015179:Colorectal Neoplasms / Q000235:genetics*; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D017353:Gene Deletion; D019254:Genes, bcl-2 / Q000235:genetics; D005838:Genotype; D006801:Humans; D007413:Intestinal Mucosa / Q000502:physiology; D018895:Microsatellite Repeats; D018807:Polymorphism, Single-Stranded Conformational; D012016:Reference Values
D004273:DNA, Neoplasm