THE MXI1 TUMOR-SUPPRESSOR GENE IS NOT MUTATED IN PRIMARY PROSTATE-CANCER

For prostate cancer, allelic deletions from the long arm of chromosome 10 (#10q23-25), the locus of the putative tumor suppressor gene MXI1 (#10q24-25), have been identified as a frequently occuring genetic eve nt. During the development of several human malignancies, the c-myc pr oto-oncogene has been identified to enhance cellular transformation, m itogenesis and cell proliferation. The MXI1 gene, belonging to the hel ix-loop-helix (bHLH) gene family, was demonstrated to display tumor su ppressor function by antagonizing c-myc induced transcriptional activi ties. Due to the detection of point mutations in the retained alleles of four primary adenocarcinomas of the prostate, MXI1 gene alterations have been suggested to be involved in the development and/or the prog ression of prostate cancer. To evaluate the role of MXI1 gene alterati ons for the development of adenocarcinoma of the prostate, 42 primary prostate cancers of different stage (T1-4) and histological grade (G(1 -3)) were investigated for alterations within exons 4 and 5 of the MXI 1 gene (spanning 6 exons in total), encoding for the functional HLH-Zi p domain, by RNA-SSCP analysis and direct PCR-DNA-sequencing following the microscopically guided tumor cell dissection from 5 mu m fresh-fr ozen buffer-soaked tissue sections. Even by application of this highly elaborated technical approach, MXI1 gene alterations could not be det ected in any of the tumor specimens investigated. Therefore, a substan tial involvement of MXI1 gene alterations in the development of prosta te cancer appears unlikely. The newly identified putative tumor suppre ssor gene PTEN, located at #10q23, might be responsible for the freque ntly observed allelic deletions from #19q23-25 in prostate cancer.