Amplifications of oncogenic genes are often considered actionable. However, not all patients respond. Questions have therefore arisen regarding the degree to which amplifications, especially non-focal ones, mediate overexpression. We found that a subset of high-level gene amplifications (≥ 6 copies) (from The Cancer Genome Atlas database) was not over-expressed at the RNA level. Unexpectedly, focal amplifications were more frequently silenced than non-focal amplifications. Most non-focal amplifications were not silenced; therefore, non-focal amplifications, if over-expressed, may be therapeutically tractable. Furthermore, specific silencing of high-level focal or non-focal gene amplifications may explain resistance to drugs that target the relevant gene product.
CITATION STYLE
Boichard, A., Lippman, S. M., & Kurzrock, R. (2021, December 1). Therapeutic implications of cancer gene amplifications without mRNA overexpression: silence may not be golden. Journal of Hematology and Oncology. BioMed Central Ltd. https://doi.org/10.1186/s13045-021-01211-1
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