Assignment of GALGT encoding beta -1,4N-acetylgalactosaminyl-transferase (GalNAc-T) and KIF5A encoding neuronal kinesin (D12S1889) to human chromosome band 12q13 by assignment to ICI YAC 26EG10 and in situ hybridization

A locus including the genes GLI, DDIT3, LRP1, SAS and CDK4 on 12q13 is frequently amplified in gliomas and sarcomas. We have now mapped two further genes, beta -1,4 N-acetylgalactosaminyltransferase (GALGT) and human neuronal kinesin (KIF5A, D12S1889), to the same region. More specifically, GALGT and KIF5A map to the same 200-kb yeast artificial chromosome as GLI and DDIT3. beta -1,4N-acetylgalactosaminyltransferase (GM2/GD2 synthase) is an enzyme involved in the synthesis of complex gangliosides which have been suggested to have a role in neuronal functioning. Human neuronal kinesin is a member of the kinesin gene family. These proteins are involved in numerous cellular processes including organelle transport, maintenance of the endoplasmic reticulum, intermediate filament distribution, organisation of spindle microtubules, chromosome segregation, flagellar growth and positioning of developmental morphogens. GLI is the human homologue of the Drosophila gene Cubitus interruptus (Ci), which is a transcription factor involved in the hedgehog signalling pathway, controlling cell fates and patterning in development. It has recently been demonstrated in Drosophila that a cytoplasmic protein, Cos2 binds to microtubules and associates with Ci thereby directly controlling its activity. It is of interest that the human homologue of Cos2 is actually human neuronal kinesin (or Kinesin HC) which we have now discovered maps to within, at most, 200 kb of GLI, its putative binding partner. beta -1,4N-Acetylgalactosaminyltransferase and neuronal kinesin are involved in neuronal cellular functioning and both map to a region known to be amplified in certain tumours. This data raises the possibility that these neuronally expressed genes are also amplified in malignancies, particularly gliomas.