Frequent loss of imprinting of IGF2 and MEST in lung adenocarcinoma.
Genomic imprinting is a parental origin-specific chromosomal modification that causes differential expression of maternal and paternal alleles of a gene. Accumulating evidence suggests that deregulation of imprinted genes, including loss of imprinting (LOI), plays a role in oncogenesis. In the present study, we investigated allelic expression of six imprinted genes in human lung adenocarcinomas as well as in matched normal lung tissue. Informative cases showing heterozygosity for the gene of interest were selected from 35 patients. LOI of the insulin-like growth factor 2 gene (IGF2) and mesoderm-specific transcript (MEST, also known as paternally expressed gene 1) was noted in 47% (seven of 15) and 85% (11 of 13) of informative cases, respectively. Monoallelic expression was maintained in all the matched normal tissues examined. LOI of IGF2 was seen more frequently in moderately to poorly differentiated adenocarcinomas. In contrast, H19, small nuclear ribonucleoprotein-associated polypeptide N gene (SNRPN), necdin gene (NDN), and long QT intronic transcript 1 (LIT1) exhibited consistent monoallelic expression in all the informative samples. These findings indicated that independent deregulation took place in imprinted genes and suggested that aberrant imprinting of IGF2 and MEST was involved in the development of lung adenocarcinoma.
Kohda
M
M
Core Research for Evolutional Science and Technology (CREST) Program, Japan Science and Technology (JST) Corporation, Department of Molecular and Cell Genetics, School of Life Sciences, Tottori University, Nishimachi 86, Yonago, Tottori 683-8503, Japan.
Hoshiya
H
H
Katoh
M
M
Tanaka
I
I
Masuda
R
R
Takemura
T
T
Fujiwara
M
M
Oshimura
M
M
D000230:Adenocarcinoma / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D001324:Autoantigens / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018392:Genomic Imprinting; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000235:genetics*; D008175:Lung Neoplasms / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D011506:Proteins / Q000235:genetics*; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000235:genetics; D017411:Ribonucleoproteins, Small Nuclear; D055517:snRNP Core Proteins
D001324:Autoantigens; C094335:H19 long non-coding RNA; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D011506:Proteins; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D017411:Ribonucleoproteins, Small Nuclear; C526417:SNRPN protein, human; C103637:mesoderm specific transcript protein; C069766:necdin; D055517:snRNP Core Proteins; D007335:Insulin-Like Growth Factor II