Diversity of EML4-ALK fusion variants in non-small cell lung cancer
10.3760/cma.j.issn.1009-9158.2012.07.004
- VernacularTitle:非小细胞肺癌EML4-ALK融合方式的多样性
- Author:
Hongxia TIAN
;
Yilong WU
;
Xuchao ZHANG
;
Shiliang CHEN
;
Weibang GUO
;
Jianguang CHEN
;
Zhi XIE
;
Ying HUANG
;
Jian SU
;
Zhihong CHEN
;
Shejuan AN
;
Hongyan TANG
- Publication Type:Journal Article
- Keywords:
Lung neoplasms;
Carcinoma,non-small-cell lung;
Oncogene proteins,fusion;
Protein-tyrosine kinases;
Polymerase chain reaction;
Mutation
- From:
Chinese Journal of Laboratory Medicine
2012;35(7):593-597
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the fusion sequence complexity of EML4-ALK in non-small cell lung cancer (NSCLC) patients,and the potential mutation in tyrosine kinase ( TK ) domain of ALK gene.MethodsIn routine practice,a novel echinoderm microtubule-associated protein-like4 and anaplastic lymphoma kinase (EML4-ALK) V3c variant was detected by rapid amplification of cDNA ends-polymerase chain reaction ( RACE-PCR )-sequencing technology in a patient with NSCLC.The further consecutive 39 cases( total of 40 cases)were screened by use of reverse transcription (RT)-PCR for EML4-ALK fusion.Positive PCR products were purified and cloned into T vectors,transformed into DH5a germ cells and colony picked up and sequenced for sequence complexity analysis.Tyrosine kinase domain of ALK was amplified by RT-PCR and sequenced.ResultsThree out of 40 cases had EML4-ALK fusion.One case had six novel variants of EML4-ALK co-existing,termed as V3c ( 64.6％ ),V3d ( 25.0％ ),V3e ( 2.1％ ),V3f (4.2％ ),V3g(2.1％ )and V3h(2.1％ ) variants,whereas without common V3a and V3b variants.In other two positive cases,one was V1 variant,another was concurrent V2,V3a and V3b variants.No mutations were detected in the TK domain of EML4-ALK in any case.ConclusionsSeveral EML-ALK variants could co-exist in a given lung cancer tissue,which suggest that the diversity and sequence complexity of EML4-ALK fusion are exist.Attentions should be paid to screen all the variants in clinic to improve the pick-up rate.
