Loss of methylation at chromosome 11p15.5 is common in human adult tumors.
Chromosome 11p15 deletion is frequent in human tumors, suggesting the presence of at least one tumor suppressor gene within this region. While mutation analyses of local genes revealed only rare mutations, we have previously described a mechanism, gain of imprinting, that leads to loss of expression of genes located on the maternal 11p15 chromosome in human hepatocarcinomas. Loss of expression was often associated with loss of maternal-specific methylation at the KvDMR1 locus. Here, we show that loss of the maternal KvDMR1 methylation is common, ranging from 30 to 50%, to a variety of adult neoplasms, including liver, breast, cervical and gastric carcinomas. We found that other 11p15.5 loci were concomitantly hypomethylated, indicating that loss of KvDMR1 methylation occurred in the context of a common mechanism affecting the methylation of a large 11p15 subchromosomal domain. These epigenetic abnormalities were not detected in any normal somatic tissue. Therefore, it seems possible that, contrary to the repression of promoter activity caused by hypermethylation, loss of gene expression at 11p15.5 may result from the activation, by hypomethylation, of one or more negative regulatory elements.
Scelfo
Rosaria A M
RA
Dipartimento di Medicina Sperimentale e Diagnostica, Università di Ferrara, Via Luigi Borsari 46, 44100 Ferrara, Italy.
Schwienbacher
Christine
C
Veronese
Angelo
A
Gramantieri
Laura
L
Bolondi
Luigi
L
Querzoli
Patrizia
P
Nenci
Italo
I
Calin
George A
GA
Angioni
Adriano
A
Barbanti-Brodano
Giuseppe
G
Negrini
Massimo
M
D000328:Adult; D002648:Child; D002880:Chromosomes, Human, Pair 11; D018899:CpG Islands; D019175:DNA Methylation; D006801:Humans; D019656:Loss of Heterozygosity; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism; D009396:Wilms Tumor / Q000235:genetics / Q000378:metabolism