作者
Ferdinandos Skoulidis, Lauren A Byers, Lixia Diao, Vassiliki A Papadimitrakopoulou, Pan Tong, Julie Izzo, Carmen Behrens, Humam Kadara, Edwin R Parra, Jaime Rodriguez Canales, Jianjun Zhang, Uma Giri, Jayanthi Gudikote, Maria A Cortez, Chao Yang, Youhong Fan, Michael Peyton, Luc Girard, Kevin R Coombes, Carlo Toniatti, Timothy P Heffernan, Murim Choi, Garrett M Frampton, Vincent Miller, John N Weinstein, Roy S Herbst, Kwok-Kin Wong, Jianhua Zhang, Padmanee Sharma, Gordon B Mills, Waun K Hong, John D Minna, James P Allison, Andrew Futreal, Jing Wang, Ignacio I Wistuba, John V Heymach
发表日期
2015/8/1
期刊
Cancer discovery
卷号
5
期号
8
页码范围
860-877
出版商
American Association for Cancer Research
简介
The molecular underpinnings that drive the heterogeneity of KRAS-mutant lung adenocarcinoma are poorly characterized. We performed an integrative analysis of genomic, transcriptomic, and proteomic data from early-stage and chemorefractory lung adenocarcinoma and identified three robust subsets of KRAS-mutant lung adenocarcinoma dominated, respectively, by co-occurring genetic events in STK11/LKB1 (the KL subgroup), TP53 (KP), and CDKN2A/B inactivation coupled with low expression of the NKX2-1 (TTF1) transcription factor (KC). We further revealed biologically and therapeutically relevant differences between the subgroups. KC tumors frequently exhibited mucinous histology and suppressed mTORC1 signaling. KL tumors had high rates of KEAP1 mutational inactivation and expressed lower levels of immune markers, including PD-L1. KP tumors demonstrated higher levels of somatic …
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F Skoulidis, LA Byers, L Diao, VA Papadimitrakopoulou… - Cancer discovery, 2015