title: Deletion of Ptprd and Cdkn2a cooperate to accelerate tumorigenesis.
abstract: PTPRD encodes the protein tyrosine phosphatase receptor type D and is frequently inactivated across many human cancers. Despite its frequent inactivation, it is unknown whether loss of PTPRD promotes tumorigenesis in vivo. PTPRD is located on chromosome 9p, as is CDKN2A, and the two loci are frequently deleted together. Here, we show that co-deletion of Ptprd and Cdkn2a cooperate to accelerate tumorigenesis. Interestingly,heterozygous loss of Ptprd was sufficient to promote tumorigenesis in our model, suggesting that Ptprd may be a haploinsufficient tumor suppressor. The loss of Ptprd resulted in changes to the tumor spectrum in mice and increased the frequency of lymphomas. In total, we reveal that Ptprd is a tumor suppressor that can promote tumorigenesis in concert with Cdkn2a loss.
authors.affiliation: Gerstner Sloan-Kettering Graduate School, Memorial Sloan-Kettering Cancer Center, New York, NY, USA; Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors.forename: Berenice
authors.initials: B
authors.lastname: Ortiz
authors.affiliation: The Tri-Institutional Laboratory of Comparative Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors.forename: Julie R
authors.initials: JR
authors.lastname: White
authors.affiliation: Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors.forename: Wei H
authors.initials: WH
authors.lastname: Wu
authors.affiliation: Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, NY, USA; Dept. of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York, USA; Brain Tumor Center, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Chan
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000235:genetics / Q000378:metabolism; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D060005:Genotyping Techniques; D006801:Humans; D019656:Loss of Heterozygosity; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2 / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D012509:Sarcoma / Q000235:genetics* / Q000378:metabolism
chemical_list: C417743:Cdkn2a protein, mouse; D019941:Cyclin-Dependent Kinase Inhibitor p16; C090899:PTPRD protein, human; C490395:Ptprd protein, mouse; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2