Frequent DNA hypomethylation of human juxtacentromericBAGE loci in cancer
2005; Wiley; Volume: 43; Issue: 1 Linguagem: Inglês
10.1002/gcc.20155
ISSN1098-2264
AutoresChristoph Grunau, Cecilia G. Sánchez, Melanie Ehrlich, Pierre van der Bruggen, Winfried Hindermann, Carmen Rodrı́guez, Sophie Krieger, Louis Dubeau, Emerich S. Fiala, Albertina De Sario,
Tópico(s)RNA Interference and Gene Delivery
ResumoThe BAGE (B melanoma antigens) sequence family contains 15 nearly identical sequences that are in the juxtacentromeric regions of chromosomes 9, 13, 18, and 21. BAGE loci are expressed in male germ tissue and in a high percentage of cancers and cancer cell lines. We analyzed the DNA methylation state of the sequences in or near the promoters of the BAGE loci by a quantitative bisulfite and PCR-based assay (multiplex COBRA) using MboI and HphI in 18 somatic tissue samples, 4 testis and 4 sperm samples, and 48 tumors and tumor cell lines. In 94% of the control somatic tissue samples, DNA was highly methylated in the analyzed regions. In contrast, 98% of tumor DNA samples displayed hypomethylation. Also, DNA from testes and sperm was hypomethylated in at least one of the BAGE loci. BAGE transcripts were observed in only 47% of the analyzed tumor samples. Consequently, we propose BAGE hypomethylation as a new, highly informative epigenetic biomarker for the diagnosis of cancer, whose hypomethylation in cancer may be causally related to that of juxtacentromeric satellite DNA.
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