MYEOV, a gene at 11q13, is coamplified with CCND1, but epigenetically inactivated in a subset of esophageal squamous cell carcinomas.
DNA amplifications at 11q13 are frequently observed in esophageal squamous cell carcinoma (ESC) and correlate with a malignant phenotype. Although this amplicon spans a region of several megabases and harbors numerous genes, CCND1 and EMS1 are thought to be the relevant candidates in ESC. We investigated whether the putative transforming gene MYEOV, mapping 360 kb centromeric to CCND1 and activated concomitantly with CCND1 in a subset of t(11;14)(q13;q32) positive multiple myeloma cell lines, represents a target of 11q13 amplification in ESC. To evaluate the role of MYEOV in ESC, we tested 31 ESC cell lines and 48 primary tumors for copy number levels of MYEOVand demonstrated that MYEOV was always coamplified with CCND1. However, MYEOV expression levels correlated only inconsistently with DNA amplification data. Treatment with the demethylating agent 5-aza-2'-deoxycytidine restored MYEOV expression in a subset of cell lines exhibiting DNA amplification without high MYEOV expression, suggesting that MYEOV is transcriptionally silenced by a DNA methylation mechanism in most of the latter cell lines. Our results indicate that MYEOV is a coamplified gene with CCND1 at 11q13, but its activation is sometimes inhibited by an epigenetic mechanism.
Janssen
Johannes W G
JW
Institute of Human Genetics, Ruprecht-Karls-University Heidelberg, Heidelberg, Germany.
Imoto
Issei
I
Inoue
Jun
J
Shimada
Yutaka
Y
Ueda
Masakazu
M
Imamura
Masayuki
M
Bartram
Claus R
CR
Inazawa
Johji
J
D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015152:Blotting, Northern; D015139:Blotting, Southern; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D019938:Cyclin D1 / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation / Q000187:drug effects; D000077209:Decitabine; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology; D005784:Gene Amplification / Q000235:genetics*; D020868:Gene Silencing / Q000187:drug effects; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics*; D015513:Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D011518:Proto-Oncogene Proteins; D014407:Tumor Cells, Cultured / Q000187:drug effects*
C407245:MYEOV protein, human; D009363:Neoplasm Proteins; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D019938:Cyclin D1; D000077209:Decitabine; D001374:Azacitidine