Derepression of Cancer/Testis Antigens in cancer is associated with distinct patterns of DNA

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dc.contributor.authorKim, Robert
dc.contributor.authorKulkarni, Prakash
dc.contributor.authorHannenhalli, Sridhar
dc.date.accessioned2014-04-01T12:19:33Z
dc.date.available2014-04-01T12:19:33Z
dc.date.issued2013-03-22
dc.descriptionPMC3618251en_US
dc.description.abstractBACKGROUND: The Cancer/Testis Antigens (CTAs) are a heterogeneous group of proteins whose expression is typically restricted to the testis. However, they are aberrantly expressed in most cancers that have been examined to date. Broadly speaking, the CTAs can be divided into two groups: the CTX antigens that are encoded by the X-linked genes and the non-X CT antigens that are encoded by the autosomes. Unlike the non-X CTAs, the CTX antigens form clusters of closely related gene families and their expression is frequently associated with advanced disease with poorer prognosis. Regardless however, the mechanism(s) underlying their selective derepression and stage-specific expression in cancer remain poorly understood, although promoter DNA demethylation is believed to be the major driver. METHODS: Here, we report a systematic analysis of DNA methylation profiling data from various tissue types to elucidate the mechanism underlying the derepression of the CTAs in cancer. We analyzed the methylation profiles of 501 samples including sperm, several cancer types, and their corresponding normal somatic tissue types. RESULTS: We found strong evidence for specific DNA hypomethylation of CTA promoters in the testis and cancer cells but not in their normal somatic counterparts. We also found that hypomethylation was clustered on the genome into domains that coincided with nuclear lamina-associated domains (LADs) and that these regions appeared to be insulated by CTCF sites. Interestingly, we did not observe any significant differences in the hypomethylation pattern between the CTAs without CpG islands and the CTAs with CpG islands in the proximal promoter. CONCLUSION: Our results corroborate that widespread DNA hypomethylation appears to be the driver in the derepression of CTA expression in cancer and furthermore, demonstrate that these hypomethylated domains are associated with the nuclear lamina-associated domains (LADS). Taken together, our results suggest that wide-spread methylation changes in cancer are linked to derepression of germ-line-specific genes that is orchestrated by the three dimensional organization of the cancer genome.en_US
dc.description.sponsorshipJH Libraries Open Access Funden_US
dc.identifier.citationdoi: 10.1186/1471-2407-13-144.en_US
dc.identifier.issn1471-2407
dc.identifier.urihttp://jhir.library.jhu.edu/handle/1774.2/36720
dc.language.isoen_USen_US
dc.publisherBioMed Centralen_US
dc.relation.ispartofseriesBMC Cancer;v. 13 p. 144
dc.subjectTestisen_US
dc.subjectNeoplasmsen_US
dc.subjectGenes, X-Linkeden_US
dc.subjectGene Expression Regulationen_US
dc.subjectNeoplasticen_US
dc.subjectDNA Methylationen_US
dc.subjectAntigensen_US
dc.subjectNeoplasmen_US
dc.titleDerepression of Cancer/Testis Antigens in cancer is associated with distinct patterns of DNAen_US
dc.typeArticleen_US
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