Journal
CANCER CELL
Volume 34, Issue 2, Pages 242-+Publisher
CELL PRESS
DOI: 10.1016/j.ccell.2018.06.013
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Funding
- G.G.'s startup funds from MGH [1S10OD012027-01A1]
- NIH [P50 CA101942-13, R01CA149738]
- Paul C. Zamecnik Chair in Oncology at the MGH Cancer Center
- Cancer Prevention and Research Institute of Texas award [RP150596]
- Career Development Award from the NCI [K08CA160658]
- Cancer Prevention & Research Institute of Texas [RR140084]
- Disease-Oriented Clinical Scholar Award (DOCS) from UT Southwestern Medical Center
- St. Baldrick's Foundation Scholar Award [524523]
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Hurthle 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.
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