Mitochondrial DNA somatic mutations (point mutations and large deletions) and mitochondrial DNA variants in human thyroid pathology - A study with emphasis on Hurthle cell tumors

• Tipo: Artigo em Revista Científica Internacional
• Data: 2002

Autores

Maximo, V (Autor) Outra; Soares, P (Autor) FMUP; Lima, J (Autor) Outra; Cameselle Teijeiro, J (Autor) Outra; Sobrinho Simoes, M (Autor) FMUP

Revista

Título: American Journal of Pathology

Vol. 160

Páginas: 1857-1865

ISSN: 0002-9440

Editora: Elsevier

Indexação

ISI Web of Knowledge - 204 Citações

Scopus - 241 Citações

Classificação Científica

FOS: Ciências médicas e da saúde > Medicina básica

Outras Informações

ID Authenticus: P-000-PCP

DOI: 10.1016/s0002-9440(10)61132-7

Abstract (EN): In an attempt to progress in the understanding of the relationship of mitochondrial DNA (mtDNA) alterations and thyroid tumorigenesis, we studied the mtDNA in 79 benign and malignant tumors (43 Hurthle and 36 non-Hurthle cell neoplasms) and respective normal parenchyma. The mtDNA common deletion (CD) was evaluated by semiquantitative polymerase chain reaction. Somatic point mutations and sequence variants of mtDNA were searched for in 66 tumors (59 patients) and adjacent parenchyma by direct sequencing of 70% of the mitochondrial genome (including all of the 13 OXPHOS system genes). We detected 57 somatic mutations, mostly transitions, in 34 tumors and 253 sequence variants in 59 patients. Follicular and papillary carcinomas carried a significantly higher prevalence of nonsilent point mutations of complex I genes than adenomas. We also detected a significantly higher prevalence of complex I and complex IV sequence variants in the normal parenchyma adjacent to the malignant tumors. Every Hurthle cell tumor displayed a relatively high percentage (up to 16%) of mtDNA CD independently of the lesion's histotype. The percentage of deleted mtDNA molecules was significantly higher in tumors with D-loop mutations than in mtDNA stable tumors. Sequence variants of the ATPase 6 gene, one of the complex V genes thought to play a role in mtDNA maintenance and integrity in yeast, were significantly more prevalent in patients with Hurthle cell tumors than in patients with non-Hurthle cell neoplasms. We conclude that mtDNA variants and mtDNA somatic mutations of complex I and complex IV genes seem to be involved in thyroid tumorigenesis. Germline polymorphisms of the ATPase 6 gene are associated with the occurrence of mtDNA CD, the hallmark of Hurthle cell tumors.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 9