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

Gastroenterology. 1999 Oct;117(4):831-7. doi: 10.1016/s0016-5085(99)70341-0.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alleles*
  • Apoptosis / genetics
  • Cell Line
  • Chromosome Mapping*
  • Chromosomes, Human, Pair 22 / genetics*
  • Colon / physiology
  • Colorectal Neoplasms / genetics*
  • DNA Mutational Analysis
  • DNA, Neoplasm / genetics
  • Gene Deletion
  • Genes, bcl-2 / genetics
  • Genotype
  • Humans
  • Intestinal Mucosa / physiology
  • Microsatellite Repeats
  • Polymorphism, Single-Stranded Conformational
  • Reference Values


  • DNA, Neoplasm

Associated data

  • GENBANK/AF174421
  • GENBANK/AF174422
  • GENBANK/AF174423
  • GENBANK/AF174424