Osteosarcoma, the most common primary malignant tumour of bone, affects both children and adults. No fundamental biological differences between paediatric and adult osteosarcoma are known. Here, we apply multi-region whole-genome sequencing to an index case of a 4-year-old child whose aggressive tumour harboured high-level, focal amplifications of MYC and CCNE1 connected by translocations. We reanalysed copy number readouts of 258 cases of high-grade osteosarcoma from three different cohorts and identified a significant enrichment of focal MYC, but not CCNE1, amplifications in children. Furthermore, we identified four additional cases of MYC and CCNE1 coamplification, highlighting a rare driver event which warrants further investigation. Our findings indicate that amplification of the MYC oncogene is a major driver of childhood osteosarcoma, while CCNE1 appears recurrently amplified independent of age.
Keywords: CCNE1; MYC; copy number variants; genomics; osteosarcoma.
© 2021 The Authors. The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and Ireland & John Wiley & Sons, Ltd.