Fusion of EML4 and ALK is associated with development of lung adenocarcinomas lacking EGFR and KRAS mutations and is correlated with ALK expression

Molecular Cancer

Research

Mike Zhu¹  Shirley Zhang¹  Xiaolin Zhang¹  Lucy Yin¹  Shiliang Chen²  Shejuan An²  Jinji Yang²  Qing Zhou²  Yi-long Wu²  Xuening Yang²  Jiaying Lin²  Zhi Xie²  Xuchao Zhang² 

[1] Guangdong General Hospital-AstraZeneca Innovation Center China Joint Laboratory, 510080, Guangzhou, China;Medical Research Center of Guangdong General Hospital, Guangdong Lung Cancer Institute, Guangdong Academy of Medical Sciences, 510080, Guangzhou, China;Guangdong General Hospital-AstraZeneca Innovation Center China Joint Laboratory, 510080, Guangzhou, China;

关键词: Anaplastic Lymphoma Kinase;    KRAS Mutation;    Anaplastic Large Cell Lymphoma;    EGFR Mutation;    Anaplastic Lymphoma Kinase Inhibitor;   

DOI  :  10.1186/1476-4598-9-188

 received in 2010-01-13, accepted in 2010-07-13,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundThe anaplastic lymphoma kinase (ALK) gene is frequently involved in translocations that lead to gene fusions in a variety of human malignancies, including lymphoma and lung cancer. Fusion partners of ALK include NPM, EML4, TPM3, ATIC, TFG, CARS, and CLTC. Characterization of ALK fusion patterns and their resulting clinicopathological profiles could be of great benefit in better understanding the biology of lung cancer.ResultsRACE-coupled PCR sequencing was used to assess ALK fusions in a cohort of 103 non-small cell lung carcinoma (NSCLC) patients. Within this cohort, the EML4-ALK fusion gene was identified in 12 tumors (11.6%). Further analysis revealed that EML4-ALK was present at a frequency of 16.13% (10/62) in patients with adenocarcinomas, 19.23% (10/52) in never-smokers, and 42.80% (9/21) in patients with adenocarcinomas lacking EGFR and KRAS mutations. The EML4-ALK fusion was associated with non-smokers (P = 0.03), younger age of onset (P = 0.03), and adenocarcinomas without EGFR/KRAS mutations (P = 0.04). A trend towards improved survival was observed for patients with the EML4-ALK fusion, although it was not statistically significant (P = 0.20). Concurrent deletion in EGFR exon 19 and fusion of EML4-ALK was identified for the first time in a Chinese female patient with an adenocarcinoma. Analysis of ALK expression revealed that ALK mRNA levels were higher in tumors positive for the EML-ALK fusion than in negative tumors (normalized intensity of 21.99 vs. 0.45, respectively; P = 0.0018). However, expression of EML4 did not differ between the groups.ConclusionsThe EML4-ALK fusion gene was present at a high frequency in Chinese NSCLC patients, particularly in those with adenocarcinomas lacking EGFR/KRAS mutations. The EML4-ALK fusion appears to be tightly associated with ALK mRNA expression levels. RACE-coupled PCR sequencing is a highly sensitive method that could be used clinically for the identification of EML4-ALK-positive patients.

【 授权许可】

Unknown   
© Zhang et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.