小柯机器人

近日，瑞士洛桑大学Giovanni Ciriello团队揭示人类癌症中的功能进化依赖性。这一研究成果于2020年9月28日在线发表在国际学术期刊《自然—遗传学》上。

Title: Discovering functional evolutionary dependencies in human cancers

Author: Marco Mina, Arvind Iyer, Daniele Tavernari, Franck Raynaud, Giovanni Ciriello

Issue&Volume: 2020-09-28

Abstract: Cancer cells retain genomic alterations that provide a selective advantage. The prediction and validation of advantageous alterations are major challenges in cancer genomics. Moreover, it is crucial to understand how the coexistence of specific alterations alters response to genetic and therapeutic perturbations. In the present study, we inferred functional alterations and preferentially selected combinations of events in >9,000 human tumors. Using a Bayesian inference framework, we validated computational predictions with high-throughput readouts from genetic and pharmacological screenings on 2,000 cancer cell lines. Mutually exclusive and co-occurring cancer alterations reflected, respectively, functional redundancies able to rescue the phenotype of individual target inhibition, or synergistic interactions, increasing oncogene addiction. Among the top scoring dependencies, co-alteration of the phosphoinositide 3-kinase (PI3K) subunit PIK3CA and the nuclear factor NFE2L2 was a synergistic evolutionary trajectory in squamous cell carcinomas. By integrating computational, experimental and clinical evidence, we provide a framework to study the combinatorial functional effects of cancer genomic alterations. Computational analysis of over 9,000 cancer genomes, coupled with functional validation in cell lines, highlights combinations of mutations required for tumor progression. This integrated approach provides a framework to stratify patients on the basis of interdependent genetic aberrations.

DOI: 10.1038/s41588-020-0703-5

Source: https://www.nature.com/articles/s41588-020-0703-5

Nature Genetics：《自然—遗传学》，创刊于1992年。隶属于施普林格·自然出版集团，最新IF：41.307
官方网址：https://www.nature.com/ng/
投稿链接：https://mts-ng.nature.com/cgi-bin/main.plex