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Deletion of Ptprd and Cdkn2a cooperate to accelerate tumorigenesis.

Ortiz B, White JR, Wu WH, Chan TA - Oncotarget (2014)

Bottom Line: PTPRD encodes the protein tyrosine phosphatase receptor type D and is frequently inactivated across many human cancers.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.

View Article: PubMed Central - PubMed

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.

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.

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Related in: MedlinePlus

Genetic patterns of PTPRD loss in human cancers(A) Histogram of the frequency of mutation and copy number loss of PTPRD in human cancers. Point mutations, heterozygous loss, and homozygous deletions are presented. Data from the cBio Portal. (B) Histogram of the frequency of PTPRD and CDKN2A inactivation (mutation and deletion) in human cancers. Data from the cBio Portal.
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Figure 1: Genetic patterns of PTPRD loss in human cancers(A) Histogram of the frequency of mutation and copy number loss of PTPRD in human cancers. Point mutations, heterozygous loss, and homozygous deletions are presented. Data from the cBio Portal. (B) Histogram of the frequency of PTPRD and CDKN2A inactivation (mutation and deletion) in human cancers. Data from the cBio Portal.

Mentions: We reviewed several genomic studies to define patterns of PTPRD loss in cancer. As shown in Figure 1A, PTPRD inactivation via deletion or mutation occurs frequently. In tumors with PTPRD copy number loss, loss of one copy of PTPRD occurs most commonly (Figure 1A). Moreover, co-deletion of PTPRD and CDKN2A occurs across a number of cancer types (Figure 1B). Co-occurrence of PTPRD and CDKN2A loss is significant across cancers (Figure 1B, p<0.05, 5 > Odds Ratio < 707, Table S1).


Deletion of Ptprd and Cdkn2a cooperate to accelerate tumorigenesis.

Ortiz B, White JR, Wu WH, Chan TA - Oncotarget (2014)

Genetic patterns of PTPRD loss in human cancers(A) Histogram of the frequency of mutation and copy number loss of PTPRD in human cancers. Point mutations, heterozygous loss, and homozygous deletions are presented. Data from the cBio Portal. (B) Histogram of the frequency of PTPRD and CDKN2A inactivation (mutation and deletion) in human cancers. Data from the cBio Portal.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4196177&req=5

Figure 1: Genetic patterns of PTPRD loss in human cancers(A) Histogram of the frequency of mutation and copy number loss of PTPRD in human cancers. Point mutations, heterozygous loss, and homozygous deletions are presented. Data from the cBio Portal. (B) Histogram of the frequency of PTPRD and CDKN2A inactivation (mutation and deletion) in human cancers. Data from the cBio Portal.
Mentions: We reviewed several genomic studies to define patterns of PTPRD loss in cancer. As shown in Figure 1A, PTPRD inactivation via deletion or mutation occurs frequently. In tumors with PTPRD copy number loss, loss of one copy of PTPRD occurs most commonly (Figure 1A). Moreover, co-deletion of PTPRD and CDKN2A occurs across a number of cancer types (Figure 1B). Co-occurrence of PTPRD and CDKN2A loss is significant across cancers (Figure 1B, p<0.05, 5 > Odds Ratio < 707, Table S1).

Bottom Line: PTPRD encodes the protein tyrosine phosphatase receptor type D and is frequently inactivated across many human cancers.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.

View Article: PubMed Central - PubMed

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.

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.

Show MeSH
Related in: MedlinePlus