Cell Res：季红斌等发现新的肺癌致病融合基因CCDC6-RET

Identification of RET gene fusion by exon array analyses in "pan-negative" lung adenocarcinomas from never smokers.

Fei Li1,*, Yan Feng1,*, Rong Fang1,*, Zhaoyuan Fang1, Jufeng Xia1, Xiangkun Han1, Xin-Yuan Liu1, Haiquan Chen2,3, Hongyan Liu1 and Hongbin Ji1

The incidence of lung cancer from never smokers has increased dramatically in China nowadays. Strikingly, approximately 30% of the lung cancer patients in East Asian population are never smokers1, 2. The majority of these patients are females with lung adenocarcinomas2. Identification of oncogenic drivers, which the tumors are “addicted to" and rely on for survival, has significantly reformed the current strategies for lung cancer treatment in clinic and initiated the era of personalized therapy3. Therapeutics specifically targeting EGFR mutations, frequently observed in never smoker patients with lung cancer, have been very helpful in improving the clinical symptoms as well as the progression-free survival4, 5, 6. Similarly, patients with lung tumors positive for ALK fusions also benefit from ALK-targeted therapy7, 8. Our previous efforts have constructed a quite comprehensive map of those essential oncogenic drivers in 52 lung adenocarcinomas from never smokers9. We have uncovered the oncognic drivers in about 90% of these lung tumors including mutations of EGFR, HER2, KRAS, as well as EML4-ALK fusion9, thus providing a strong clinical guidance for molecular-targeted therapy for this subset of disease. However, there is still about 10% (5/52) of these never smoker patients were “pan-negative” for all known oncogenic driver mutations and could not benefit from the effective targeted therapy in clinic.