Chunk #3 — Introduction — MiR-15/16 and DLEU7 at 13q14: a unique collaboration of coding and noncoding genes in indolent CLL — MiR-15/16 at 13q14, discovery and function
Since 13q14 deletions also occur in mantle cell lymphoma, myeloma, and prostate cancer [1, 2], it is possible that one or more tumor suppressor genes at 13q14 are important in the pathogenesis of CLL and other malignancies. To identify tumor suppressor gene (or genes) at 13q14 several groups have used positional cloning, and a region of more than 1 Mb has been fully sequenced and characterized [8, 9]. However, in spite of extensive research, none of the known genes of this region were found to be inactivated in CLL by deletions, mutations or promoter hypermethylation [8–11]. In order to finally find the elusive tumor suppressor gene at 13q14, in 2001 we generated somatic cell hybrids between mouse and CLLs cells carrying 13q14 deletion and translocation. Using these hybrids we finally identified a 30-kb region of deletion between exons 2 and 5 of LEU2 gene [12, 13]. The translocation breakpoint was mapped in the same region [12]. Since LEU2 had previously been excluded as a likely candidate tumor suppressor gene in CLL [8, 9, 11, 14] we continued to search for
