Somatic mitochondrial DNA (mtDNA) mutations in papillary thyroid carcinomas and differential mtDNA sequence variants in cases with thyroid tumours

Somatic mutations in mtDNA have recently been identified in colorectal tumo urs, Studies of oncocytic tumours have led to hypotheses which propose that defects in oxidative phosphorylation may result in a compensatory increase in mitochondrial replication and/or gene expression. Mutational analysis o f mtDNA in thyroid neoplasia, which is characterised by increased numbers o f mitochondria and is also one of the most common sites of oncocytic tumour s, has been limited to date. Using the recently developed technique of two- dimensional gene scanning, me have successfully examined 21 cases of thyroi d tumours, six cases of nonneoplastic thyroid pathology, 30 population cont rols, nine foetal thyroid tissues and nine foetal tissues of nonthyroid ori gin, either kidney or liver. We have identified three different somatic mut ations (23%) in papillary thyroid carcinomas. In addition, we have found si gnificant differential distributions of mtDNA sequence variants between thy roid carcinomas and controls. Interestingly, these variants appear to be mo re frequent in the genes which encode complex I of the mitochondrial electr on transport chain compared to normal population controls, These findings s uggest first, that somatic mtDNA mutations may be involved in thyroid tumor igenesis and second, that the accumulation of certain non-somatic variants may be related to tumour progression in the thyroid.