Ptprj is a candidate for the mouse colon-cancer susceptibility locus Scc1 and is frequently deleted in human cancers

Nat Genet. 2002 Jul;31(3):295-300. doi: 10.1038/ng903. Epub 2002 Jun 24.

Abstract

Only a small proportion of cancers result from familial cancer syndromes with Mendelian inheritance. Nonfamilial, 'sporadic' cancers, which represent most cancer cases, also have a significant hereditary component, but the genes involved have low penetrance and are extremely difficult to detect. Therefore, mapping and cloning of quantitative trait loci (QTLs) for cancer susceptibility in animals could help identify homologous genes in humans. Several cancer-susceptibility QTLs have been mapped in mice and rats, but none have been cloned so far. Here we report the positional cloning of the mouse gene Scc1 (Susceptibility to colon cancer 1) and the identification of Ptprj, encoding a receptor-type protein tyrosine phosphatase, as the underlying gene. In human colon, lung and breast cancers, we show frequent deletion of PTPRJ, allelic imbalance in loss of heterozygosity (LOH) and missense mutations. Our data suggest that PTPRJ is relevant to the development of several different human cancers.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / pathology
  • Animals
  • Breast Neoplasms / genetics
  • Cell Cycle Proteins / chemistry
  • Cell Cycle Proteins / genetics*
  • Chromosomal Proteins, Non-Histone
  • Chromosome Mapping
  • Colonic Neoplasms / chemically induced
  • Colonic Neoplasms / genetics*
  • Dimethylhydrazines
  • Gene Deletion
  • Gene Silencing
  • Genetic Markers
  • Humans
  • Loss of Heterozygosity
  • Lung Neoplasms / genetics
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred Strains
  • Nuclear Proteins
  • Phosphoproteins
  • Polymorphism, Genetic
  • Protein Tyrosine Phosphatases / genetics*
  • Quantitative Trait, Heritable
  • Receptor-Like Protein Tyrosine Phosphatases, Class 3
  • Saccharomyces cerevisiae Proteins
  • Sequence Homology, Amino Acid
  • Sequence Homology, Nucleic Acid

Substances

  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone
  • Dimethylhydrazines
  • Genetic Markers
  • MCD1 protein, S cerevisiae
  • Nuclear Proteins
  • Phosphoproteins
  • Saccharomyces cerevisiae Proteins
  • PTPRJ protein, human
  • Protein Tyrosine Phosphatases
  • Ptprj protein, mouse
  • Receptor-Like Protein Tyrosine Phosphatases, Class 3