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Chromosome 1 rearrangements involving the genes TPR and NTRK1 produce structurally different thyroid-specific TRK oncogenes.

Abstract
The NTRK1 gene in the q arm of chromosome 1 encodes one of the receptors for the nerve growth factor and is frequently activated as an oncogene in papillary thyroid carcinomas. The activation is due to chromosomal rearrangements juxtaposing the NTRK1 tyrosine kinase domain to 5'-end sequences from different genes. The thyroid TRK oncogenes are activated by recombination with at least three different genes: the gene coding for tropomyosin and TPR, both on chromosome 1,and TFG on chromosome 3. In a previous study, we showed that two tumors carrying the TPR/NTRK1 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 rearrangements in two thyroid tumors, and (3) a detailed analysis of the three different TPR/NTRK1 rearrangements. With molecular studies based on Southern 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 rearrangement involving sequences derived from chromosome 17 was detected.
AuthorsA Greco, C Miranda, S Pagliardini, L Fusetti, I Bongarzone, M A Pierotti
JournalGenes, chromosomes & cancer (Genes Chromosomes Cancer) Vol. 19 Issue 2 Pg. 112-23 (Jun 1997) ISSN: 1045-2257 [Print] United States
PMID9172002 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Nuclear Pore Complex Proteins
  • Proto-Oncogene Proteins
  • Receptors, Nerve Growth Factor
  • TPR protein, human
  • Receptor Protein-Tyrosine Kinases
  • Receptor, trkA
Topics
  • Base Sequence
  • Chromosomes, Human, Pair 1
  • Cloning, Molecular
  • Gene Rearrangement
  • Humans
  • Molecular Sequence Data
  • Nuclear Pore Complex Proteins
  • Oncogenes
  • Proto-Oncogene Proteins (genetics)
  • Receptor Protein-Tyrosine Kinases (genetics)
  • Receptor, trkA
  • Receptors, Nerve Growth Factor (genetics)
  • Sequence Analysis, DNA
  • Sequence Homology, Nucleic Acid
  • Thyroid Neoplasms (genetics)
  • Tumor Cells, Cultured

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