Identification of kinase fusion oncogenes in post-Chernobyl radiation-induced thyroid cancers Academic Article uri icon

Overview

MeSH Major

  • Carcinoma
  • Chernobyl Nuclear Accident
  • Mutation
  • Neoplasms, Radiation-Induced
  • Oncogene Fusion
  • Thyroid Neoplasms

abstract

  • Exposure to ionizing radiation during childhood markedly increases the risk of developing papillary thyroid cancer. We examined tissues from 26 Ukrainian patients with thyroid cancer who were younger than 10 years of age and living in contaminated areas during the time of the Chernobyl nuclear reactor accident. We identified nonoverlapping somatic driver mutations in all 26 cases through candidate gene assays and next-generation RNA sequencing. We found that 22 tumors harbored fusion oncogenes that arose primarily through intrachromosomal rearrangements. Altogether, 23 of the oncogenic drivers identified in this cohort aberrantly activate MAPK signaling, including the 2 somatic rearrangements resulting in fusion of transcription factor ETS variant 6 (ETV6) with neurotrophic tyrosine kinase receptor, type 3 (NTRK3) and fusion of acylglycerol kinase (AGK) with BRAF. Two other tumors harbored distinct fusions leading to overexpression of the nuclear receptor PPARĪ³. Fusion oncogenes were less prevalent in tumors from a cohort of children with pediatric thyroid cancers that had not been exposed to radiation but were from the same geographical regions. Radiation-induced thyroid cancers provide a paradigm of tumorigenesis driven by fusion oncogenes that activate MAPK signaling or, less frequently, a PPARĪ³-driven transcriptional program.

publication date

  • November 2013

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3809792

Digital Object Identifier (DOI)

  • 10.1172/JCI69766

PubMed ID

  • 24135138

Additional Document Info

start page

  • 4935

end page

  • 44

volume

  • 123

number

  • 11