Frequent DNA hypomethylation of human juxtacentromeric BAGE loci in cancer.
The 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.
Grunau
Christoph
C
Institut de Génétique Humaine, CNRS UPR 1142, Montpellier, France.
Sanchez
Cecilia
C
Ehrlich
Melanie
M
van der Bruggen
Pierre
P
Hindermann
Winfried
W
Rodriguez
Carmen
C
Krieger
Sophie
S
Dubeau
Louis
L
Fiala
Emerich
E
De Sario
Albertina
A
D000951:Antigens, Neoplasm / Q000235:genetics*; D001943:Breast Neoplasms; D045744:Cell Line, Tumor; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D009369:Neoplasms / Q000235:genetics*; D010051:Ovarian Neoplasms; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D015183:Restriction Mapping; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013094:Spermatozoa / Q000502:physiology; D013737:Testis / Q000502:physiology / Q000503:physiopathology
D000951:Antigens, Neoplasm; C092706:BAGE protein, human; D004273:DNA, Neoplasm