Somatic and germline mutation in GRIM-19, a dual function gene involved in mitochondrial metabolism and cell death, is linked to mitochondrion-rich (Hurthle cell) tumours of the thyroid.
| Autor: | Máximo, V., Botelho, T., Capela, J., Soares, P., Lima, J., Taveira, A., Amaro, T., Barbosa, A. P., Preto, A., Harach, H. R., Williams, D., Sobrinho-Sim&öes, M., Máximo, V, Sobrinho-Simões, M |
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| Předmět: |
THYROID cancer
ONCOLOGY CELL death ANTINEOPLASTIC agents CYSTS (Pathology) CANCER genetics MITOCHONDRIAL pathology ADENOMA APOPTOSIS COMPARATIVE studies DOCUMENTATION RESEARCH methodology MEDICAL cooperation MITOCHONDRIA GENETIC mutation NUCLEOTIDES OXIDOREDUCTASES PROTEINS RESEARCH THYROID gland tumors TRANSFERASES EVALUATION research CASE-control method SEQUENCE analysis |
| Zdroj: | British Journal of Cancer; 5/23/2005, Vol. 92 Issue 10, p1892-1898, 7p |
| Abstrakt: | Oxyphil or Hurthle cell tumours of the thyroid are characterised by their consistent excessive number of mitochondria. A recently discovered gene, GRIM-19 has been found to fulfil two roles within the cell: as a member of the interferon-beta and retinoic acid-induced pathway of cell death, and as part of the mitochondrial Complex I assembly. In addition, a gene predisposing to thyroid tumours with cell oxyphilia (TCO) has been mapped to chromosome 19p13.2 in one family. A cluster of genes involved in mitochondrial metabolism occurs in this region; one of these is GRIM-19. We have searched for GRIM-19 mutations in a series of 52 thyroid tumours. Somatic missense mutations in GRIM-19 were detected in three of 20 sporadic Hurthle cell carcinomas. A germline mutation was detected in a Hurthle cell papillary carcinoma arising in a thyroid with multiple Hurthle cell nodules. No mutations were detected in any of the 20 non-Hurthle cell carcinomas tested, nor in any of 96 blood donor samples. In one of the sporadic Hurthle cell papillary carcinomas positive for GRIM-19 mutation, we have also detected a ret/PTC-1 rearrangement. No GRIM-19 mutations were detected in any of the six cases of known familial Hurthle cell tumour tested, so that our results do not support the identification of GRIM-19 as the TCO gene. The GRIM-19 mutations we have detected are the first nuclear gene mutations specific to Hurthle cell tumours to be reported to date; we propose that such mutations can be involved in the genesis of sporadic or familial Hurthle cell tumours through the dual function of GRIM-19 in mitochondrial metabolism and cell death. [ABSTRACT FROM AUTHOR] |
| Databáze: | Complementary Index |
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