Ptprj is a candidate for the mouse colon-cancer susceptibility locus Scc1 and is frequently deleted in human cancers.
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.
Ruivenkamp
Claudia A L
CA
Division of Molecular Genetics, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
van Wezel
Tom
T
Zanon
Carlo
C
Stassen
Alphons P M
AP
Vlcek
Cestmir
C
Csikós
Tamás
T
Klous
Anita M
AM
Tripodis
Nikos
N
Perrakis
Anastassis
A
Boerrigter
Lucie
L
Groot
Peter C
PC
Lindeman
Jan
J
Mooi
Wolter J
WJ
Meijjer
Gerrit A
GA
Scholten
Gert
G
Dauwerse
Hans
H
Paces
Vaclav
V
van Zandwijk
Nico
N
van Ommen
Gert Jan B
GJ
Demant
Peter
P
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
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