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Published on: July 27, 2019

Proximity of TPR and NTRK1 rearranging loci in human thyrocytes

Emanuela Roccato1, Paola Bressan, Guido Sabatella

  • 1Department of Experimental Oncology Operative Unit Molecular Mechanisms of Cancer Growth and Progression, Istituto Nazionale Tumori, Milan, Italy.

Cancer Research
|April 5, 2005
PubMed

Insights

Thyroid cancer involves gene rearrangements. Researchers found that proximity of specific gene loci in thyroid cells, compared to blood cells, may increase the risk of these cancer-associated rearrangements.

Area of Science:

  • Genetics
  • Cancer Biology
  • Molecular Oncology

Background:

  • Chromosomal rearrangements are common in cancer, but their cell-type specificity is unclear.
  • Papillary thyroid carcinomas frequently exhibit rearrangements of RET and NTRK1 tyrosine kinase receptor genes, forming oncogenes.
  • Previous work suggests spatial proximity of RET and H4 loci in thyrocytes favors recombination.

Purpose of the Study:

  • To investigate if spatial proximity of the NTRK1 gene and its oncogenic partner TPR contributes to thyroid-specific TRK oncogene formation.
  • To compare the spatial arrangement of these loci in thyroid cells versus peripheral blood lymphocytes.

Main Methods:

  • Two-color fluorescence in situ hybridization (FISH) was used to determine the distance between NTRK1 and TPR loci.
  • Two-dimensional microscopy and three-dimensional reconstruction of FISH data were employed.
  • Spatial distances were analyzed in thyrocytes and peripheral blood lymphocytes.

Main Results:

  • The distance between the NTRK1 and TPR loci was significantly reduced in thyrocytes compared to peripheral blood lymphocytes.
  • This spatial proximity in thyrocytes supports a mechanism for enhanced gene rearrangement.

Conclusions:

  • Spatial proximity of translocation-prone gene loci, like NTRK1 and TPR, in thyrocytes may favor the generation of oncogenic rearrangements.
  • This finding contributes to understanding the cell-type specificity of chromosomal rearrangements in cancer.

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