The CCDC6-RET Fusion — A Novel Oncogenic Driver in Lung Adenocarcinoma

Identification of oncogenic drivers has significantly reformed the current strategies for lung cancer treatment in clinic and initiated the era of personalized therapy. Previous efforts have uncovered oncogenic drivers in approximately 90% of lung adenocarcinomas from never smokers and the rest 10% were considered as "pan-negative" tumors. Recently, a team of researchers led by Dr. JI Hongbin, at Shanghai Institute of Biochemistry and Cell Biology (SIBCB), Shanghai Institutes for Biological Sciences, CAS, have identified a novel oncogenic driver, the CCDC6-RET gene fusion, in these "pan-negative" lung adenocarcinomas.

 

Research in the JI lab mainly focus on lung cancer genomics studies and aim to identify essential oncogenic drivers via systematic genomic analyses. Through exon array analyses followed by molecular studies on those "pan-negative" tumors, LI Fei together with other students in the lab has successfully identified a new oncogenic driver, the fusion of CCDC6 to RET (CCDC6 exon 1 fused to RET exon 12), in lung cancer. RET is a receptor tyrosine kinase and its fusion has been previously reported only in papillary thyroid carcinomas but not in any other type of cancers. The genomic translocation of CCDC6 to RET has resulted in a high expression of the RET kinase domain which may contribute to lung tumorigenesis. This study may provide an important therapeutic target for lung cancer treatment in clinic.

 

This work entitled “Identification of RET gene fusion by exon array analyses in "pan-negative" lung adenocarcinomas from never smokers” was published online in Cell Research on February 21^st, 2012.

 

This study was supported by grants from the Chinese Academy of Sciences, the National Basic Research Program of China, the National Natural Science Foundation of China, and the Key Construction Program of the National “985” Project.

 

AUTHOR CONTACT:

JI Hongbin

Shanghai 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

 

A spectrum of oncogenic drivers is constructed for the cohort containing 52 lung adenocarcinomas from never smokers: EGFR mutations (78.8%), HER2 mutations (3.8%), KRAS mutations (1.9%), EML4-ALK fusions (5.8%), CD74-ROS1 fusion (1.9%) and CCDC6-RET fusion (1.9%). In these mutations, CCDC6-RET is a novel oncogenic driver mutation.

(Image provided by Dr. JI Hongbin)