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.
Keywords: Hurthle cell carcinoma; copy-number alterations; fusion genes; genomics; mitochondrial mutations; transcriptome.
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