Unknown,Transcriptomics,Genomics,Proteomics

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Identification of ZDHHC14 as a novel tumor suppressor gene commonly downregulated in human cancers

ABSTRACT: Genomic changes affecting tumor suppressor genes (TSGs) are fundamental to cancer. We applied SNP array analysis on a panel of testicular germ cell tumors (TGCTs) to search for novel TSGs and identified a frequent small deletion on 6q25.3 containing just one gene; ZDHHC14. The expression of ZDHHC14, a putative protein palmitoyltransferase, was decreased both at RNA and protein levels in TGCTs and this decrease correlated with chemoresistance. ZDHHC14 expression was also significantly decreased in a panel of prostate cancer samples and cell lines. Through next generation sequencing of the ZDHHC14 genomic locus we discovered several mutations in both cancer types, confirming the clinical significance of our findings. Furthermore, inducible overexpression of ZDHHC14 led to reduced cell viability and increased apoptosis through the classic caspase-dependent apoptotic pathway. Finally, we confirmed our in vitro findings of the tumor suppressor role of ZDHHC14 in a mouse xenograft model, showing that overexpression of ZDHHC14 inhibits tumorigenesis. Thus we have identified a novel TSG that is commonly downregulated in human tumors, as well as given mechanistic insight into the functional role of ZDHHC14, a potential protein palmitoyltransferase about which almost nothing has been described in the literature. Copy number analysis of Affymetrix 10K SNP array was performed for a total of 36 testicular germ cell tumour cases.Five samples have case-matched normal controls. All unpaired samples were compared with a common normal control, which was generated from the five normal samples.

ORGANISM(S): Homo sapiens

SUBMITTER: Xueying Mao

PROVIDER: E-GEOD-35216 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Identification of ZDHHC14 as a novel tumor suppressor gene commonly downregulated in human cancers

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