TY - JOUR
T1 - Gain of imprinting at chromosome 11p15
T2 - A pathogenetic mechanism identified in human hepatocarcinomas
AU - Schwienbacher, Christine
AU - Gramantieri, Laura
AU - Scelfo, Rosaria
AU - Veronese, Angelo
AU - Calin, George A.
AU - Bolondi, Luigi
AU - Croce, Carlo M.
AU - Barbanti-Brodano, Giuseppe
AU - Negrini, Massimo
PY - 2000/5/9
Y1 - 2000/5/9
N2 - 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.
AB - 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.
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U2 - 10.1073/pnas.090087497
DO - 10.1073/pnas.090087497
M3 - Article
C2 - 10779553
AN - SCOPUS:0034625042
SN - 0027-8424
VL - 97
SP - 5445
EP - 5449
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 10
ER -