Format

Send to

Choose Destination
See comment in PubMed Commons below
J Clin Invest. 2013 Nov;123(11):4935-44. doi: 10.1172/JCI69766. Epub 2013 Oct 25.

Identification of kinase fusion oncogenes in post-Chernobyl radiation-induced thyroid cancers.

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 PPARγ. 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 PPARγ-driven transcriptional program.

PMID:
24135138
PMCID:
PMC3809792
DOI:
10.1172/JCI69766
[Indexed for MEDLINE]
Free PMC Article

Publication types, MeSH terms, Substances, Supplementary concept, Secondary source ID, Grant support

Publication types

MeSH terms

Substances

Supplementary concept

Secondary source ID

Grant support

PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for American Society for Clinical Investigation Icon for PubMed Central
    Loading ...
    Support Center