PLX145815

GSE48850: Novel kinase fusion oncogenes in post-Chernobyl radiation-induced pediatric thyroid cancers

• Organsim human
• Type RNASEQ
• Target gene
• Project ARCHS4

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 PPAR. 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 PPAR-driven transcriptional program. SOURCE: Christopher MasonChristopher Mason Lab Weill Cornell Medical College