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
DOI/URL:
Notes: Article -- Export Date: 4 September 2018 -- Source: Scopus
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MSK Authors
  1. Venkatraman Ennapadam Seshan
    283 Seshan
  2. James A Fagin
    105 Fagin
  3. Timothy Chan
    206 Chan
  4. Ronald A Ghossein
    292 Ghossein
  5. Eric J Sherman
    146 Sherman
  6. Nadeem Riaz
    205 Riaz
  7. Luc Morris
    122 Morris
  8. Yiyu Dong
    16 Dong
  9. Ian Ganly
    227 Ganly
  10. Eduard Reznik
    32 Reznik
  11. Vladimir Makarov
    30 Makarov
  12. Promita   Bose
    7 Bose
  13. Stephanie Lauren Eng
    2 Eng
  14. Fengshen Kuo
    6 Kuo