CHROMOSOME-I REARRANGEMENTS INVOLVING THE GENES TPR AND NTRK1 PRODUCESTRUCTURALLY DIFFERENT THYROID-SPECIFIC TRK ONCOGENES

The NTRK1 gene in the q arm of chromosome 1 encodes one of the recepto rs for the nerve growth factor and is frequently activated as an oncog ene in papillary thyroid carcinomas. The activation is due to chromoso mal rearrangements juxtaposing the NTRK1 tyrosine kinase domain to 5'- end sequences from different genes. The thyroid TRK oncogenes are acti vated by recombination with at least three different genes: the gene c oding for tropomyosin and TPR, both on chromosome 1, and TFG on chromo some 3. In a previous study, we showed that two tumors carrying the TP RINTRK1 rearrangement contained structurally different oncogenes named TRK-T1 and TRK-T2. In this paper, we report (1) the cDNA structure of TRK-T2, (2) evidence that TRK-T2 is generated by different rearrangem ents in mo thyroid tumors, and (3) a detailed analysis of the three di fferent TPRINTRK1 rearrangements. With molecular studies based on Sout hern blot hybridization, cloning, and sequencing, we show that all the rearrangements are nearly balanced, involving deletion, insertion, or duplication of only few nucleotides. In one case, an additional rearr angement involving sequences derived from chromosome 17 was detected. (C) 1997 Wiley-Liss, Inc.