BACKGROUND & AIMS: 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.
BACKGROUND & AIMS: 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 humancolorectal 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 humancolorectal carcinogenesis. The identification of a 0.5-cM interval serves as the basis for the isolation of such a gene by positional cloning.
Authors: Paola Alberici; Emma de Pater; Joana Cardoso; Mieke Bevelander; Lia Molenaar; Jos Jonkers; Riccardo Fodde Journal: Am J Pathol Date: 2007-01 Impact factor: 4.307
Authors: Cameron N Johnstone; Perry S Mongroo; A Sophie Rich; Michael Schupp; Mark J Bowser; Andrew S Delemos; John W Tobias; Yingqiu Liu; Gregory E Hannigan; Anil K Rustgi Journal: Mol Cell Biol Date: 2007-11-12 Impact factor: 4.272
Authors: Michael W Straza; Seema Paliwal; Ramesh C Kovi; Barur Rajeshkumar; Peter Trenh; Daniel Parker; Giles F Whalen; Stephen Lyle; Celia A Schiffer; Steven R Grossman Journal: Cell Cycle Date: 2010-09-08 Impact factor: 4.534