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.
Highlights
Protein tyrosine phosphatase receptor type D (PTPRD) is a tumor suppressor gene on chromosome 9p
We show that Ptprd loss promotes tumorigenesis in the setting of Cdkn2a deletion
We show that heterozygous loss of Ptprd is sufficient to promote tumorigenesis
Summary
Protein tyrosine phosphatase receptor type D (PTPRD) is a tumor suppressor gene on chromosome 9p. Despite the high prevalence of PTPRD inactivation in human tumors, it is not known whether loss of PTPRD directly promotes tumorigenesis in vivo. The CDKN2A gene produces the p16Ink4a and p14/p19Arf tumor suppressors [12]. We and others have shown that selective pressure exists for inactivation of both genes on chromosome 9p, by deletion or mutation [8,10,11,13,14]. Despite the potential role of PTPRD loss in cancer, Ptprd deficient mice do not spontaneously develop tumors [15]. 69% of Cdkn2a-/- mice develop tumors at an average age of 29 weeks [16]. We generated Ptprd/Cdkn2a co-deleted mice to determine if Ptprd loss contributes to tumorigenesis
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