Cloning, expression and chromosomal location of NKX6B to 10q26, a region frequently deleted in brain tumors

Nkx6-2 (former Gtx) is a murine-homeobox-containing gene localized distally on Chromosome (Chr) 7. Analysis of the expression pattern, together with D NA binding assays, suggests that this gene product might be important for d ifferentiated oligodendrocyte function and in the regulation of myelin gene expression. We now report on the cloning and characterization of the human homolog (NKX6B). DNA sequence analysis of an 11-kb genomic fragment reveal ed that the complete human gene spans 1.2 kb and is composed of three exons . NKX6B is predicted to encode a polypeptide of 277 amino acids with 97% id entity to mouse Nkx6-2. Northern blot experiments showed that NKX6B express ion is tightly controlled in a tissue-specific fashion with the highest sit e of expression being the brain. Finally, using STS content mapping and RH analyis, we demonstrated that NKX6B maps to the 10q26, a region where frequ ent loss of heterozygosity has been observed in various malignant brain tum ors. These results may implicate NKX6B as a candidate tumor suppressor gene for brain tumors, particularly for oligodendrogliomas.