Disruptive mitochondrial DNA mutations in complex I subunits are markers of oncocytic phenotype in thyroid tumors
Proceedings of the National Academy of Sciences of the United States of America, ISSN: 0027-8424, Vol: 104, Issue: 21, Page: 9001-9006
2007
- 239Citations
- 104Captures
- 3Mentions
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Metrics Details
- Citations239
- Citation Indexes238
- 238
- CrossRef198
- Patent Family Citations1
- 1
- Captures104
- Readers104
- 104
- Mentions3
- References3
- 3
Article Description
Oncocytic tumors are a distinctive class of proliferative lesions composed of cells with a striking degree of mitochondrial hyperplasia that are particularly frequent in the thyroid gland. To understand whether specific mitochondrial DNA (mtDNA) mutations are associated with the accumulation of mitochondria, we sequenced the entire mtDNA in 50 oncocytic lesions (45 thyroid tumors of epithelial cell derivation and 5 mitochondrion-rich breast tumors) and 52 control cases (21 nononcocytic thyroid tumors, 15 breast carcinomas, and 16 gliomas) by using recently developed technology that allows specific and reliable amplification of the whole mtDNA with quick mutation scanning. Thirteen oncocytic lesions (26%) presented disruptive mutations (nonsense or frameshift), whereas only two samples (3.8%) presented such mutations in the nononcocytic control group. In one case with multiple thyroid nodules analyzed separately, a disruptive mutation was found in the only nodule with oncocytic features. In one of the five mitochondrion-rich breast tumors, a disruptive mutation was identified. All disruptive mutations were found in complex I subunit genes, and the association between these mutations and the oncocytic phenotype was statistically significant (P = 0.001). To study the pathogenicity of these mitochondrial mutations, primary cultures from oncocytic tumors and corresponding normal tissues were established. Electron microscopy and biochemical and molecular analyses showed that primary cultures derived from tumors bearing disruptive mutations failed to maintain the mutations and the oncocytic phenotype. We conclude that disruptive mutations in complex I subunits are markers of thyroid oncocytic tumors. © 2007 by The National Academy of Sciences of the USA.
Bibliographic Details
http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=34547480470&origin=inward; http://dx.doi.org/10.1073/pnas.0703056104; http://www.ncbi.nlm.nih.gov/pubmed/17517629; https://pnas.org/doi/full/10.1073/pnas.0703056104; https://dx.doi.org/10.1073/pnas.0703056104; https://www.pnas.org/content/104/21/9001
Proceedings of the National Academy of Sciences
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