The Majority of Chinese Lung Adenocarcinoma Patients from Never Smokers could Benefit from Targeted Therapy

Lung cancer is the leading cause of cancer-related death worldwide. If lung cancer from never smokers was considered as a separate category, the disease would rank among seven to nine most common fatal cancers in the US and the fifth most common malignancies in China. Identification of oncogenic drivers in these lung tumors, which the tumors are "addicted to" and rely on for survival, have significantly reformed the current strategies for cancer treatment in clinic and initiated the era of personalized therapy. Previous work from Dr. JI Hongbin’s group have uncovered the essential oncogenic drivers in approximately 90% of samples in just four genes: EGFR, KRAS, HER2, and ALK (Sun et al, JCO, 2010). However, it is unknown whether there exists other oncogenic drivers and this high prevalence of known oncogenic drivers is accurate in a large setting of clinical specimens.

 

With the continuous efforts and collaboration with Fudan University Shanghai Cancer Center, the JI lab have recently investigated the oncogenic drivers including the newly defined ROS1 fusion in 202 lung adenocarcinomas from never smokers. Consistent with previous work, current data have shown that 89.1% of samples harbored mutations in genes of EGFR, KRAS, HER2, ALK and ROS1. Patients with EGFR mutations tend to be older than those without EGFR mutations (58.3 Vs 54.3, P=0.016) and patients without any known oncogenic driver tend to be diagnosed at a younger age (52.3 Vs 57.9, P=0.013). These data indicate that the majority of never smokers with lung adenocarcinoma could benefit from treatment with a specific tyrosine kinase inhibitor.

 

This work entitled “Spectrum of Oncogenic Driver Mutations in Lung Adenocarcinomas from East Asian Never Smokers” was published online in PLoS ONE on Nov 30^th, 2011.

 

This study was supported by the grants from the Chinese Academy of Sciences, National Natural Science Foundation of China and Shanghai Municipal Commission for Science and Technology.

 

AUTHOR CONTACT:

JI Hongbin

Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences

Shanghai, China

Phone:86-21-54921108; E-mail: hbji@sibs.ac.cn

 

Mutation spectrum of lung adenocarcinoma from never smokers and ROS1 fusion detection.
(A) Spectrum of oncogenic driver mutations in lung adenocarcinomas from never smokers. From 202 tumors, 75.3% (152/202) harbored EGFR kinase domain mutations, 5.9% (12/202) HER2 mutations, 5.0% (10/202) ALK fusions, and 2% (4/202) KRAS mutations, 1% (2/202) of tumors harbor ROS1 fusion. There are 10.9% (22/202) with unknown oncogenic driver mutations.
(B) Agarose gel electrophoresis analysis of RT-PCR products for CD74-ROS1 fusions. E32, CD74-ROS1 exon 32 fusion; E34, CD74-ROS1 exon 34 fusion.
(C) Sequencing of RT-PCR product from a tumor (No.72) identified a fusion of CD74 exon 6 to ROS1 exon 34.
(D) Sequencing of RT-PCR product from a tumor (No.136) identified a fusion of CD74 exon 6 to both ROS1 exon 32 and exon 34. (Image provided by Dr. JI Hongbin)