GENOMIC CHARACTERIZATION OF THE HUMAN TRKC GENE

The trkC gene encodes the high-affinity receptor for neurotrophin 3 an d plays an important role in the regulation of the survival and differ entiation of the mammalian nervous system and in heart development. Ch romosomal rearrangements of trkC have been recently reported in congen ital fibrosarcoma and it has been proposed that abnormal activation of this gene might be involved in tumor development. To facilitate the s earch for new mutations and rearrangements in the human trkC locus we have partially characterized its genomic organization by restriction m apping and have obtained the complete intron-exon structure. Our resul ts show that human trkC consists of 20 exons, including two that encod e the inserts present in the extracellular and tyrosine kinase domains , and another two that encode the carboxyl-terminal tail of the trunca ted TRKC isoform. Analysis of the 5' flanking region revealed the abse nce of TATA box, a very high content in C/G compatible with a CpG isla nd and the presence of putative binding sites for the AP1, AP2, GC, AT F, BRN2, AML1 and Nkx2.5 transcription factors.