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Novel kinase fusion oncogenes in post-Chernobyl radiation-induced pediatric thyroid cancers

ABSTRACT: Exposure to ionizing radiation during childhood markedly increases the risk of developing papillary thyroid cancer. We identified non-overlapping somatic driver mutations in all 26 cases of post-Chernobyl thyroid cancers we studied through candidate gene assays and next generation RNA-sequencing. We found that 22/26 harbored fusion oncogenes arising primarily through intrachromosomal rearrangements. Altogether 23/26 of the oncogenic drivers identified in this cohort aberrantly activate MAPK signaling, including the two novel somatic rearrangements ETV6-NTRK3 and AGK-BRAF. Two other tumors harbored distinct fusions leading to overexpression of the nuclear receptor PPARγ. A lower prevalence of fusion oncogenes was found in a cohort of pediatric thyroid cancers from children from the same geographical regions that were not exposed to radiation. Radiation-induced thyroid cancers are a paradigm of tumorigenesis driven by fusion oncogenes that activate MAPK signaling or, less frequently, a PPARγ-driven transcriptional program.

ORGANISM(S): Homo sapiens

PROVIDER: GSE48850 | GEO | 2013/10/25

SECONDARY ACCESSION(S): PRJNA211959

REPOSITORIES: GEO

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Novel kinase fusion oncogenes in post-Chernobyl radiation-induced pediatric thyroid cancers

Project description:Exposure to ionizing radiation during childhood markedly increases the risk of developing papillary thyroid cancer. We identified non-overlapping somatic driver mutations in all 26 cases of post-Chernobyl thyroid cancers we studied through candidate gene assays and next generation RNA-sequencing. We found that 22/26 harbored fusion oncogenes arising primarily through intrachromosomal rearrangements. Altogether 23/26 of the oncogenic drivers identified in this cohort aberrantly activate MAPK signaling, including the two novel somatic rearrangements ETV6-NTRK3 and AGK-BRAF. Two other tumors harbored distinct fusions leading to overexpression of the nuclear receptor PPARγ. A lower prevalence of fusion oncogenes was found in a cohort of pediatric thyroid cancers from children from the same geographical regions that were not exposed to radiation. Radiation-induced thyroid cancers are a paradigm of tumorigenesis driven by fusion oncogenes that activate MAPK signaling or, less frequently, a PPARγ-driven transcriptional program. Examination of transcriptome profiles and genetic somatic changes in thyroid cancer.

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