Chunk #6 — Introduction — MiR-15/16 and DLEU7 at 13q14: a unique collaboration of coding and noncoding genes in indolent CLL — DLEU7, a second tumor suppressor at 13q14
Recently, a high-resolution map of 13q14 deletions using 171 CLL samples was reported [18]. These study used microarray based technology to determine the minimal deleted region at 13q14 in CLL. Interestingly, in addition to miR-15/16, this region also contained DLEU7 gene located telometic to miR-15/16 [18], and previously identified as a candidate tumor suppressor gene at 13q14 [19]. DLEU7 encodes a 221 amino acid protein with no homology to known proteins. Sequencing of DLEU7 coding exons failed to find mutations in 45 CLL samples, although DLEU7 promoter was methylated in 61% of CLL [19]. Since DLEU7 is the only protein coding gene located within the minimal deleted region at 13q14, very recently we investigated whether DLEU7 can function as a tumor suppressor and cooperate with miR-15/16 [20]. We first examined expression of DLEU7 in CLL samples and normal CD19+ B-cells by real time RT-PCR results. All CLL samples examined showed decreased DLEU7 expression, while over 50% showed decrease of ten fold or more. Expression of both, miR-15 and miR-16, was also decreased in over 90% of CLL samples examined [20].