Disease relevance of DNAJC15

• Methylation-dependent transcriptional silencing of MCJ has been observed in ovarian cancers and associated with increased resistance to chemotherapeutic agents; however, its role in other cancer types has not been widely investigated [1].
• Extensive methylation patterns were associated with the methylation-dependent transcriptional silencing of MCJ in medulloblastoma and stPNET cell lines [1].
• We examined the status of MCJ in intracranial primitive neuroectodermal tumours [PNETs, comprising cerebellar PNETs (medulloblastomas) and supratentorial PNETs (stPNETs)] and ependymomas, together representing the most common malignant brain tumours of childhood [1].
• 5'CpG of BCL2L10 and DNAJD1 was hypermethylated in 4 of 5 gastric cancer cell lines, whereas 5'CpG of DKK1 was hypermethylated in only 1 cell line [2].

High impact information on DNAJC15

• Further investigations of the mechanism of MCJ inactivation revealed that its loss could occur either through biallelic epigenetic methylation or by methylation in association with genetic loss of its second allele [1].
• Of these, we could determine the methylation status of 5'CpG islands of BCL2L10, DKK1 and DNAJD1 [2].
• The MCJ CpG island is methylated and the gene is not expressed in cells of epithelial origin, but unmethylated and expressed in cells of lymphocyte or fibroblast origin [3].
• Cell type-specific methylation of an intronic CpG island controls expression of the MCJ gene [3].
• Loss of expression of the MCJ gene has previously been linked to increased chemotherapeutic drug resistance in ovarian cancer [3].

Biological context of DNAJC15

• Chromatin immunoprecipitation assays determined that MCJ CpG island methylation was associated with loss of histone acetylation in ovarian epithelial cells compared with unmethylated fibroblast cells [3].
• We report that loss of expression of MCJ in drug-resistant ovarian cancer cell lines depends on methylation of a CpG island within its first exon, but is independent of methylation within the promoter region [3].
• The other series (MCJ, 109 age-matched case-control pairs) showed significant (p=0.003) association with these haplotypes [4].

Anatomical context of DNAJC15

• Normal ovarian surface epithelial cells are methylated at the MCJ CpG island and do not express the MCJ gene [5].

Associations of DNAJC15 with chemical compounds

• METHODS: The methylation status of 35 CpG sites within the MCJ CpG island was determined by sequencing of sodium bisulfite modified tumor DNA in 41 patients with stage III/IV epithelial ovarian tumors [5].

Other interactions of DNAJC15

• Furthermore, cell type-specific expression of the MCJ gene in normal cells also depends on the methylation status of the CpG island within its first exon [3].

Analytical, diagnostic and therapeutic context of DNAJC15

• Arthrography of the wrist was performed on 300 consecutive patients by injecting contrast material separately into the radiocarpal (RCJ), midcarpal (MCJ), and distal radioulnar (DRUJ) joints [6].
• Demethylation of the MCJ gene in stage III/IV epithelial ovarian cancer and response to chemotherapy [5].
• To detect different expression patterns between the originally reported MCJ transcript and the LTR-related transcript, we performed a RT-PCR approach using various human tissues and cancer cells [7].

References