Expression of an endogenous retroviral sequence from the HERV-H group in gastrointestinal cancers.
Human endogenous retroviruses (HERVs) account for approximately 8% of the human genome. Since the majority of HERV elements have accumulated inactivating mutations in the viral genes, only few expressed viral open reading frames (ORFs) have been described. In this study, we have analyzed the expression of a HERV-H copy located on Xp22.3 encompassing a potential ORF immediately downstream of the viral promoter. Conventional and real time RT-PCR based expression analysis of this specific HERV-H sequence showed overexpression in 16 of 34 (47%) colorectal, 25 of 63 (40%) gastric and 2 of 12 (17%) pancreatic cancers, whereas no overexpression was detected in bronchial and cervical cancers. Normal human testis, placenta and breast tissue did not show expression of this sequence. CpG methylation analysis of the viral promoter revealed a loss of methylation in cell lines expressing the HERV-H sequence as compared to nonexpressing cell lines and lymphocyte DNA derived from healthy individuals. Further investigations of the HERV-H long terminal repeat and the HERV-H RNA are necessary to assess the functional relevance of the HERV-H expression.
Wentzensen
Nicolas
N
Department of Applied Tumor Biology, Institute of Pathology, University of Heidelberg, Heidelberg, Germany. nicolas.wentzensen@med.uni-heidelberg.de
Coy
Johannes F
JF
Knaebel
Hanns-Peter
HP
Linnebacher
Michael
M
Wilz
Birgit
B
Gebert
Johannes
J
von Knebel Doeberitz
Magnus
M
D000595:Amino Acid Sequence; D001483:Base Sequence; D045744:Cell Line, Tumor; D041321:Chromosomes, Human, X / Q000235:genetics; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D020077:Endogenous Retroviruses / Q000235:genetics*; D005770:Gastrointestinal Neoplasms / Q000235:genetics* / Q000473:pathology; D015870:Gene Expression; D006801:Humans; D008957:Models, Genetic; D008969:Molecular Sequence Data