Genomic imprinting of IGF-II and H19 in adult human pancreatic tissues.
OBJECTIVE
Genomic imprinting is a chromosomal modification causing differential expression of maternal and paternal alleles. Loss of imprinting (LOI) of IGF-II and H19 has been suggested to be an early oncogenic event in cancerogenesis. Aim of the present study was to describe the status of IGF-II and H19 imprinting in adult human pancreatic tissues.


METHODS
Allele-specific gene expression was studied using RNA and DNA from human pancreatic cancer, chronic pancreatitis, and normal pancreas tissues heterozygous for ApaI (IGF-II) or RsaI (H19) restriction fragment length polymorphism. Reverse-transcriptase polymerase chain reaction products were digested with either ApaI or RsaI and analyzed on agarose gels to study the status of allelic expression. The expression level of H19 and IGF-II was studied on Northern blots or by polymerase chain reaction.


RESULTS
H19 was imprinted in normal pancreas and in chronic pancreatitis. H19 LOI was observed in 1 of 4 informative cancer tissues and was not associated with increased H19 transcript levels. Biallelic expression of IGF-II was found in 6 of 10 informative cancer tissues and in 6 of 9 informative normal tissues. In chronic pancreatitis, the IGF-II gene was imprinted in all informative samples. IGF-II mRNA was not overexpressed in the tissues showing LOI.


CONCLUSIONS
Low frequencies of H19 LOI and the lack of correlation between biallelic expression and overexpression observed for both H19 and IGF-II suggest that LOI of H19 and IGF-II is not a relevant oncogenic factor during human exocrine pancreatic cancerogenesis.
Micha
A E
AE
Department of Internal Medicine I, University of Ulm, Germany.
Hähnel
S
S
Friess
H
H
Büchler
M W
MW
Adler
G
G
Gress
T M
TM
D000230:Adenocarcinoma / Q000235:genetics; D000328:Adult; D000483:Alleles; D015152:Blotting, Northern; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor / Q000235:genetics*; D018392:Genomic Imprinting; D006579:Heterozygote; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000235:genetics*; D009124:Muscle Proteins / Q000235:genetics*; D010179:Pancreas / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000235:genetics*; D010195:Pancreatitis / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D020133:Reverse Transcriptase Polymerase Chain Reaction
C094335:H19 long non-coding RNA; D009124:Muscle Proteins; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D007335:Insulin-Like Growth Factor II