Integrated Genomic Analysis of Hürthle Cell Cancer Reveals Oncogenic Drivers, Recurrent Mitochondrial Mutations, and Unique Chromosomal Landscapes.

Research paper by Ian I Ganly, Vladimir V Makarov, Shyamprasad S Deraje, YiYu Y Dong, Ed E Reznik, Venkatraman V Seshan, Gouri G Nanjangud, Stephanie S Eng, Promita P Bose, Fengshen F Kuo, Luc G T LGT Morris, Inigo I Landa, Pedro Blecua PB Carrillo Albornoz, Nadeem N Riaz, Yuri E YE Nikiforov, et al.

Indexed on: 15 Aug '18Published on: 15 Aug '18Published in: Cancer Cell


The molecular foundations of Hürthle cell carcinoma (HCC) are poorly understood. Here we describe a comprehensive genomic characterization of 56 primary HCC tumors that span the spectrum of tumor behavior. We elucidate the mutational profile and driver mutations and show that these tumors exhibit a wide range of recurrent mutations. Notably, we report a high number of disruptive mutations to both protein-coding and tRNA-encoding regions of the mitochondrial genome. We reveal unique chromosomal landscapes that involve whole-chromosomal duplications of chromosomes 5 and 7 and widespread loss of heterozygosity arising from haploidization and copy-number-neutral uniparental disomy. We also identify fusion genes and disrupted signaling pathways that may drive disease pathogenesis. Copyright © 2018 Elsevier Inc. All rights reserved.