Department of Molecular Cancer Genetics, University of Strasbourg Hospitals, 67000, Strasbourg, France.
Center for Personalized Cancer Therapy, Moores Cancer Center, University of California, La Jolla, CA, 92093, USA.
J Hematol Oncol. 2021 Dec 2;14(1):201. doi: 10.1186/s13045-021-01211-1.
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.
致癌基因的扩增通常被认为是有治疗作用的。然而，并非所有患者都有反应。因此，人们对扩增（尤其是非焦点扩增）介导过表达的程度提出了质疑。我们发现，一组高水平的基因扩增（≥6 个拷贝）（来自癌症基因组图谱数据库）在 RNA 水平上没有过表达。出乎意料的是，焦点扩增比非焦点扩增更常被沉默。大多数非焦点扩增并未被沉默；因此，如果过表达，非焦点扩增可能具有治疗潜力。此外，高水平焦点或非焦点基因扩增的特异性沉默可能解释了对靶向相关基因产物的药物的耐药性。
