title: Gain of imprinting at chromosome 11p15: A pathogenetic mechanism identified in human hepatocarcinomas.
abstract: Genomic imprinting is a reversible condition that causes parental-specific silencing of maternally or paternally inherited genes. Analysis of DNA and RNA from 52 human hepatocarcinoma samples revealed abnormal imprinting of genes located at chromosome 11p15 in 51% of 37 informative samples. The most frequently detected abnormality was gain of imprinting, which led to loss of expression of genes present on the maternal chromosome. As compared with matched normal liver tissue, hepatocellular carcinomas showed extinction or significant reduction of expression of one of the alleles of the CDKN1C, SLC22A1L, and IGF2 genes. Loss of maternal-specific methylation at the KvDMR1 locus in hepatocarcinoma correlated with abnormal expression of CDKN1C and IGF2, suggesting a function for KvDMR1 as a long-range imprinting center active in adult tissues. These results point to the role of epigenetic mechanisms leading to loss of expression of imprinted genes at chromosome region 11p15 in human tumors.
authors.affiliation: Dipartimento di Medicina Sperimentale e Diagnostica, Università di Ferrara, via Luigi Borsari 46, 44100 Ferrara, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Schwienbacher
authors.forename: L
authors.initials: L
authors.lastname: Gramantieri
authors.forename: R
authors.initials: R
authors.lastname: Scelfo
authors.forename: A
authors.initials: A
authors.lastname: Veronese
authors.forename: G A
authors.initials: GA
authors.lastname: Calin
authors.forename: L
authors.initials: L
authors.lastname: Bolondi
authors.forename: C M
authors.initials: CM
authors.lastname: Croce
authors.forename: G
authors.initials: G
authors.lastname: Barbanti-Brodano
authors.forename: M
authors.initials: M
authors.lastname: Negrini
mesh_terms: D000328:Adult; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics; D019175:DNA Methylation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D019450:Genes, MDR; D018392:Genomic Imprinting; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000235:genetics; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D007335:Insulin-Like Growth Factor II