Synapse - Integrated genomic analysis of Hürthle cell cancer reveals oncogenic drivers, recurrent mitochondrial mutations, and unique chromosomal landscapes

Integrated genomic analysis of Hürthle cell cancer reveals oncogenic drivers, recurrent mitochondrial mutations, and unique chromosomal landscapes Journal Article

Authors:	Ganly, I.; Makarov, V.; Deraje, S.; Dong, Y.; Reznik, E.; Seshan, V.; Nanjangud, G.; Eng, S.; Bose, P.; Kuo, F.; Morris, L. G. T.; Landa, I.; Blecua Carrillo Albornoz, P.; Riaz, N.; Nikiforov, Y. E.; Patel, K.; Umbricht, C.; Zeiger, M.; Kebebew, E.; Sherman, E.; Ghossein, R.; Fagin, J. A.; Chan, T. A.
Article Title:	Integrated genomic analysis of Hürthle cell cancer reveals oncogenic drivers, recurrent mitochondrial mutations, and unique chromosomal landscapes
Abstract:	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. Ganly et al. elucidate recurrent mutations impacting the RTK/RAS/AKT/mTOR pathway, DNA damage/repair, epigenetic modifiers, TERT promoter, and the mitochondrial genome in Hürthle cell carcinoma (HCC). HCCs also display prevalent chromosome 5 and 7 duplications, loss of heterozygosity, and in-frame gene fusions. © 2018 Elsevier Inc.
Keywords:	genomics; transcriptome; hürthle cell carcinoma; copy-number alterations; fusion genes; mitochondrial mutations
Journal Title:	Cancer Cell
Volume:	34
Issue:	2
ISSN:	1535-6108
Publisher:	Cell Press
Date Published:	2018-08-13
Start Page:	256
End Page:	270.e5
Language:	English
DOI:	10.1016/j.ccell.2018.07.002
PROVIDER:	scopus
PUBMED:	30107176
PMCID:	PMC6247912
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85050402694&doi=10.1016%2fj.ccell.2018.07.002&partnerID=40&md5=e53ba33bf2541a0f27a3b59eeccdea39
Notes:	Article -- Export Date: 4 September 2018 -- Source: Scopus