title: Ptprj is a candidate for the mouse colon-cancer susceptibility locus Scc1 and is frequently deleted in human cancers.
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.
authors.affiliation: Division of Molecular Genetics, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
authors.forename: Claudia A L
authors.initials: CA
authors.lastname: Ruivenkamp
authors.forename: Tom
authors.initials: T
authors.lastname: van Wezel
authors.forename: Carlo
authors.initials: C
authors.lastname: Zanon
authors.forename: Alphons P M
authors.initials: AP
authors.lastname: Stassen
authors.forename: Cestmir
authors.initials: C
authors.lastname: Vlcek
authors.forename: Tamás
authors.initials: T
authors.lastname: Csikós
authors.forename: Anita M
authors.initials: AM
authors.lastname: Klous
authors.forename: Nikos
authors.initials: N
authors.lastname: Tripodis
authors.forename: Anastassis
authors.initials: A
authors.lastname: Perrakis
authors.forename: Lucie
authors.initials: L
authors.lastname: Boerrigter
authors.forename: Peter C
authors.initials: PC
authors.lastname: Groot
authors.forename: Jan
authors.initials: J
authors.lastname: Lindeman
authors.forename: Wolter J
authors.initials: WJ
authors.lastname: Mooi
authors.forename: Gerrit A
authors.initials: GA
authors.lastname: Meijjer
authors.forename: Gert
authors.initials: G
authors.lastname: Scholten
authors.forename: Hans
authors.initials: H
authors.lastname: Dauwerse
authors.forename: Vaclav
authors.initials: V
authors.lastname: Paces
authors.forename: Nico
authors.initials: N
authors.lastname: van Zandwijk
authors.forename: Gert Jan B
authors.initials: GJ
authors.lastname: van Ommen
authors.forename: Peter
authors.initials: P
authors.lastname: Demant
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000235:genetics*; D002868:Chromosomal Proteins, Non-Histone; D002874:Chromosome Mapping; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000235:genetics*; D004127:Dimethylhydrazines; D017353:Gene Deletion; D020868:Gene Silencing; D005819:Genetic Markers; D006801:Humans; D019656:Loss of Heterozygosity; D008175:Lung Neoplasms / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D009687:Nuclear Proteins; D010750:Phosphoproteins; D011110:Polymorphism, Genetic; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D019655:Quantitative Trait, Heritable; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3; D029701:Saccharomyces cerevisiae Proteins; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid
chemical_list: D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D004127:Dimethylhydrazines; D005819:Genetic Markers; C490529:MCD1 protein, S cerevisiae; D009687:Nuclear Proteins; D010750:Phosphoproteins; D029701:Saccharomyces cerevisiae Proteins; C486288:PTPRJ protein, human; D017027:Protein Tyrosine Phosphatases; C098066:Ptprj protein, mouse; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3