Characterization of a novel B-CLL candidate gene--DLEU7--located in the 13q14 tumor suppressor locus.
Deletion of chromosome 13q14 is the most frequent genetic aberration in B-cell chronic lymphocytic leukemia (CLL), found in more than 50% of cases, indicating that this region contains a gene(s) involved in the development of CLL. However, the pathogenic gene in the critical 13q14 region has not yet been defined. Here, we have cloned and characterized a novel gene, DLEU7, located adjacent to the consensus deleted region, and overlapping the 3' end of DLEU1 tail to tail. Human DLEU7 encodes a putative 221 amino acid protein, with significant conservation in rodents. Mutational and expression analysis in primary CLL samples failed to demonstrate any specific mutations in DLEU7, but no DLEU7 expression could be detected in CLL cells. Methylation of a CpG island in the promoter region of DLEU7 was further analyzed as a possible mechanism for the absence of DLEU7 expression, and the promoter was found to be methylated in the majority of the CLL samples investigated.
Hammarsund
Marianne
M
Department of Oncology/Pathology, Cancer Center Karolinska, R8:03, Karolinska Hospital and Institute, S-17176, Stockholm, Sweden.
Corcoran
Martin M
MM
Wilson
William
W
Zhu
Chaoyong
C
Einhorn
Stefan
S
Sangfelt
Olle
O
Grandér
Dan
D
D000595:Amino Acid Sequence; D000818:Animals; D015152:Blotting, Northern; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics*; D003001:Cloning, Molecular; D019175:DNA Methylation; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000235:genetics; D017353:Gene Deletion; D015973:Gene Expression Regulation, Leukemic; D016147:Genes, Tumor Suppressor; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011518:Proto-Oncogene Proteins; D051381:Rats; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D025521:Tumor Suppressor Proteins
C482307:DLEU7 protein, human; C482309:DLEU7 protein, rat; D017931:DNA Primers; C482308:Dleu7 protein, mouse; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D025521:Tumor Suppressor Proteins