Hypothetic model of oncocytic follicular thyroid carcinoma development and progression.

<p>Mutations in mtDNA underlie low levels of ATP productions. In order to compensate for these low energy levels mitochondria carrying these mutations proliferate and accumulate in the cytoplasm of affected cells. Oncocytic FTC is also characterised by a mitochondria-rich cytoplasm, are known to harbour mtDNA mutations (mainly complex I) and do show a disturbed energy production. DNA replication and progression through the cell cycle are energy demanding processes. Low energy levels might also disturb normal formation and function of the mitotic spindle, resulting in an unbalanced mitosis. Cells that have lost chromosomes during several rounds of cell division become DNA near-haploid (haploidisation process). Sustaining a near-haploid genome may require less energy than of normal 2n cells. Consequently near-haploid cells show a growth advantage and are selected for during tumour development. Maintaining chromosome 7 in heterozygous state ([AB]) seems to be essential for tumour survival. This might be indicative for the presence of genes playing an important role in oncocytic FTC. Endoreduplication of these genes into an [AABB] allelic state increases the gene dosage which might be beneficial for further progression.