| Literature DB >> 30107175 |
Raj K Gopal1, Kirsten Kübler2, Sarah E Calvo3, Paz Polak4, Dimitri Livitz5, Daniel Rosebrock5, Peter M Sadow6, Braidie Campbell7, Samuel E Donovan7, Salma Amin8, Benjamin J Gigliotti9, Zenon Grabarek3, Julian M Hess5, Chip Stewart5, Lior Z Braunstein5, Peter F Arndt5, Scott Mordecai10, Angela R Shih11, Frances Chaves10, Tiannan Zhan12, Carrie C Lubitz13, Jiwoong Kim14, A John Iafrate11, Lori Wirth15, Sareh Parangi16, Ignaty Leshchiner5, Gilbert H Daniels17, Vamsi K Mootha18, Dora Dias-Santagata11, Gad Getz19, David G McFadden20.
Abstract
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.Entities:
Keywords: Hürthle cell; chromosomal losses; complex I; haploid; loss of heterozygosity; metastasis; mitochondria; mtDNA; oncocytic; thyroid cancer
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Year: 2018 PMID： 30107175 PMCID： PMC6121811 DOI： 10.1016/j.ccell.2018.06.013
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743