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

• Tipo: Artigo em Revista Científica Internacional
• Data: 2005

Autores

Maximo, V (Autor) Outra; Botelho, T (Autor) Outra; Capela, J (Autor) Outra; Soares, P (Autor) FMUP; Lima, J (Autor) Outra; Taveira, A (Autor) Outra; Amaro, T (Autor) Outra; Barbosa, AP (Autor) Outra; Preto, A (Autor) Outra; Harach, HR (Autor) Outra; Williams, D (Autor) Outra; Sobrinho Simoes, M (Autor) FMUP

Revista

Título: British Journal of Cancer

Vol. 92

Páginas: 1892-1898

ISSN: 0007-0920

Editora: Springer Nature

Indexação

ISI Web of Knowledge - 156 Citações

Scopus - 183 Citações

Classificação Científica

FOS: Ciências médicas e da saúde > Medicina clínica

Outras Informações

ID Authenticus: P-000-39P

DOI: 10.1038/sj.bjc.6602547

Abstract (EN): 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.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 7