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Cancer Cell DOI:10.1016/j.ccell.2018.06.013

Widespread Chromosomal Losses and Mitochondrial DNA Alterations as Genetic Drivers in Hürthle Cell Carcinoma.

Publication TypeJournal Article
Year of Publication2018
AuthorsGopal, RK, Kübler, K, Calvo, SE, Polak, P, Livitz, D, Rosebrock, D, Sadow, PM, Campbell, B, Donovan, SE, Amin, S, Gigliotti, BJ, Grabarek, Z, Hess, JM, Stewart, C, Braunstein, LZ, Arndt, PF, Mordecai, S, Shih, AR, Chaves, F, Zhan, T, Lubitz, CC, Kim, J, A Iafrate, J, Wirth, L, Parangi, S, Leshchiner, I, Daniels, GH, Mootha, VK, Dias-Santagata, D, Getz, G, McFadden, DG
JournalCancer Cell
Date Published2018 08 13
KeywordsChromosome Aberrations, DNA Copy Number Variations, DNA, Mitochondrial, Haploidy, Humans, Mutation, Neoplasm Metastasis, Telomerase, Thyroid Neoplasms, Whole Exome Sequencing

Hürthle cell carcinoma of the thyroid (HCC) is a form of thyroid cancer recalcitrant to radioiodine therapy that exhibits an accumulation of mitochondria. We performed whole-exome sequencing on a cohort of primary, recurrent, and metastatic tumors, and identified recurrent mutations in DAXX, TP53, NRAS, NF1, CDKN1A, ARHGAP35, and the TERT promoter. Parallel analysis of mtDNA revealed recurrent homoplasmic mutations in subunits of complex I of the electron transport chain. Analysis of DNA copy-number alterations uncovered widespread loss of chromosomes culminating in near-haploid chromosomal content in a large fraction of HCC, which was maintained during metastatic spread. This work uncovers a distinct molecular origin of HCC compared with other thyroid malignancies.


Alternate JournalCancer Cell
PubMed ID30107175
PubMed Central IDPMC6121811
Grant ListK08 CA160658 / CA / NCI NIH HHS / United States
P50 CA101942 / CA / NCI NIH HHS / United States
R01 CA149738 / CA / NCI NIH HHS / United States
S10 OD012027 / OD / NIH HHS / United States
/ HHMI / Howard Hughes Medical Institute / United States