A functional genomic approach to actionable gene fusions for precision oncology.
A functional genomic approach to actionable gene fusions for precision oncology.
复制标题
用于精确肿瘤学的可操作基因融合的功能基因组方法。
DOI：
10.1126/sciadv.abm2382
复制
发表时间：
2022-02-11
期刊：
影响因子：
13.6
通讯作者：
Liang H
中科院分区：
文献类型：
--
作者：
Li J;Lu H;Ng PK;Pantazi A;Ip CKM;Jeong KJ;Amador B;Tran R;Tsang YH;Yang L;Song X;Dogruluk T;Ren X;Hadjipanayis A;Bristow CA;Lee S;Kucherlapati M;Parfenov M;Tang J;Seth S;Mahadeshwar HS;Mojumdar K;Zeng D;Zhang J;Protopopov A;Seidman JG;Creighton CJ;Lu Y;Sahni N;Shaw KR;Meric-Bernstam F;Futreal A;Chin L;Scott KL;Kucherlapati R;Mills GB;Liang H
融合基因是一类有吸引力的治疗靶点。已经在癌症患者中发现了数千个融合基因，但其中大多数的功能后果和治疗意义在很大程度上仍然未知。在这里，我们开发了一种功能基因组方法，包括有效的融合重建和敏感的细胞活力和药物反应分析。应用这种方法，我们对癌症基因组图谱患者样本中检测到的约100个融合基因进行了表征，揭示了显著部分低频融合对肿瘤生长具有激活作用。聚焦于RTK-RAS通路，我们确定了一些激活融合，可以显着影响对相关药物的敏感性。最后，我们提出了一个完整的证据级分类系统来系统地优先考虑基因融合。我们的研究重申了临床迫切需要采用类似的功能基因组方法来表征基因融合，从而最大化基因融合在精确肿瘤学中的效用。功能基因组方法能够有效地识别可操作的基因融合，用于精确肿瘤学。
Fusion genes represent a class of attractive therapeutic targets. Thousands of fusion genes have been identified in patients with cancer, but the functional consequences and therapeutic implications of most of these remain largely unknown. Here, we develop a functional genomic approach that consists of efficient fusion reconstruction and sensitive cell viability and drug response assays. Applying this approach, we characterize ~100 fusion genes detected in patient samples of The Cancer Genome Atlas, revealing a notable fraction of low-frequency fusions with activating effects on tumor growth. Focusing on those in the RTK-RAS pathway, we identify a number of activating fusions that can markedly affect sensitivity to relevant drugs. Last, we propose an integrated, level-of-evidence classification system to prioritize gene fusions systematically. Our study reiterates the urgent clinical need to incorporate similar functional genomic approaches to characterize gene fusions, thereby maximizing the utility of gene fusions for precision oncology. A functional genomic approach enables efficient identification of actionable gene fusions for precision oncology.
登录
查看更多内容
癌症基因组地图集中的致癌信号通路。
影响因子：
64.5
作者：
Sanchez-Vega F;Mina M;Armenia J;Chatila WK;Luna A;La KC;Dimitriadoy S;Liu DL;Kantheti HS;Saghafinia S;Chakravarty D;Daian F;Gao Q;Bailey MH;Liang WW;Foltz SM;Shmulevich I;Ding L;Heins Z;Ochoa A;Gross B;Gao J;Zhang H;Kundra R;Kandoth C;Bahceci I;Dervishi L;Dogrusoz U;Zhou W;Shen H;Laird PW;Way GP;Greene CS;Liang H;Xiao Y;Wang C;Iavarone A;Berger AH;Bivona TG;Lazar AJ;Hammer GD;Giordano T;Kwong LN;McArthur G;Huang C;Tward AD;Frederick MJ;McCormick F;Meyerson M;Cancer Genome Atlas Research Network;Van Allen EM;Cherniack AD;Ciriello G;Sander C;Schultz N
通讯作者：
Schultz N
影响因子：
64.5
作者：
Cancer Genome Atlas Research Network
通讯作者：
Cancer Genome Atlas Research Network
影响因子：
14.9
作者：
Nguyen DT;Mathias S;Bologa C;Brunak S;Fernandez N;Gaulton A;Hersey A;Holmes J;Jensen LJ;Karlsson A;Liu G;Ma'ayan A;Mandava G;Mani S;Mehta S;Overington J;Patel J;Rouillard AD;Schürer S;Sheils T;Simeonov A;Sklar LA;Southall N;Ursu O;Vidovic D;Waller A;Yang J;Jadhav A;Oprea TI;Guha R
通讯作者：
Guha R
影响因子：
14.9
作者：
Hu X;Wang Q;Tang M;Barthel F;Amin S;Yoshihara K;Lang FM;Martinez-Ledesma E;Lee SH;Zheng S;Verhaak RGW
通讯作者：
Verhaak RGW
影响因子：
4.8
作者：
Debnath, J;Muthuswamy, SK;Brugge, JS
通讯作者：
Brugge, JS