TY - JOUR
T1 - Loss of methylation at chromosome 11p15.5 is common in human adult tumors
AU - Scelfo, Rosaria A.M.
AU - Schwienbacher, Christine
AU - Veronese, Angelo
AU - Gramantieri, Laura
AU - Bolondi, Luigi
AU - Querzoli, Patrizia
AU - Nenci, Italo
AU - Calin, George A.
AU - Angioni, Adriano
AU - Barbanti-Brodano, Giuseppe
AU - Negrini, Massimo
N1 - Funding Information:
We thank Augusto Bevilacqua and Pietro Zucchini for the excellent technical assistance. RAM Scelfo is supported by a fellowship from Fondazione Italiana per la Ricerca sul Cancro (FIRC). This work was supported by grants from Associazione Italiana per la Ricerca sul Cancro (AIRC), Milan, Italy and from MURST ex-60%.
PY - 2002
Y1 - 2002
N2 - 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.
AB - 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.
KW - Chromosome 11p15.5
KW - DNA hypomethylation
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U2 - 10.1038/sj.onc.1205336
DO - 10.1038/sj.onc.1205336
M3 - Article
C2 - 11971191
AN - SCOPUS:85047699309
SN - 0950-9232
VL - 21
SP - 2564
EP - 2572
JO - Oncogene
JF - Oncogene
IS - 16
ER -