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

• Type: Article in International Scientific Journal
• Date: 2005

Authors

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

Journal

Title: British Journal of Cancer

Vol. 92

Pages: 1892-1898

ISSN: 0007-0920

Publisher: Springer Nature

Indexing

ISI Web of Knowledge - 156 Citations

Scopus - 184 Citations

Scientific classification

FOS: Medical and Health sciences > Clinical medicine

Other information

Authenticus ID: 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 7