Abstract
BackgroundThe KIF5B-RET rearrangement is detected with the frequency of 1 ~ 2 % in ‘triple marker’-negative lung adenocarcinomas, i.e., EGFR, KRAS and EML4-ALK wild type. These mutational changes are known to be mutually exclusive, but the co-existence of ALK rearrangement with activating mutations of EGFR is rarely found.MethodsWe examined the KIF5B-RET fusion gene in frozen tissues from 154 surgically resected lung tumors using RT-PCR with direct sequencing and the mutation status of EGFR and KRAS genes using PNA clamping. We tested KIF5B-RET translocation in Formalin Fixed Paraffin Embedded using fluorescence in situ hybridization. We also measured RET mRNA and protein expression by RT-PCR and immunohistochemistry, respectively.ResultsThe existence of KIF5B-RET fusion gene was identified in 9 patients. The mean age was 67.2 and M: F ratio 4:5. Of 9 patients, 3 patients harbored wild type of EGFR and KRAS gene. However, KIF5B-RET fusion gene coincided with EGFR or KRAS mutation in 6 patients. These six pts were also positive for both RET break-apart probes (23.9 %) and KIF5B-RET fusion (44.4 %). However, there were no correlations between RET mRNA and protein expression in the KIF5B-RET-positive patients. The median disease free survival and overall survival were 23.9 months and 29.5 months, respectively.ConclusionsTaken together, our data suggest one-step screening platform for KIF5B-RET as well as EGFR, K-RAS, ALK oncogenic mutations be necessary for lung adenocarcinoma patients because EGFR or KRAS mutation are not infrequently found in KIF5B-RET-positive patients.
Highlights
The Kinesin family member 5B (KIF5B)-RET rearrangement is detected with the frequency of 1 ~ 2 % in ‘triple marker’-negative lung adenocarcinomas, i.e., epidermal growth factor receptor (EGFR), KRAS and EML4-ALK wild type
Distribution of the KIF5B-RET fusion gene, and EGFR and KRAS mutations The expression of the KIF5B-RET fusion gene was analyzed in 154 archival tumor tissues
In contrast to previous reports, our results indicate that the KIF5B-RET fusion gene may coincide with EGFR or KRAS mutations, albeit at a lower frequency, in lung adenocarcinomas
Summary
The KIF5B-RET rearrangement is detected with the frequency of 1 ~ 2 % in ‘triple marker’-negative lung adenocarcinomas, i.e., EGFR, KRAS and EML4-ALK wild type. These mutational changes are known to be mutually exclusive, but the co-existence of ALK rearrangement with activating mutations of EGFR is rarely found. In 2012, we first identified the existence of the Kinesin family member 5B (KIF5B)-RET fusion gene in a young male patient with lung adenocarcinoma using wholegenome and transcriptome sequencing analysis. The KIF5B-RET fusion gene is rarely found in Asians or never smokers, and is mutually exclusive to other oncogenic mutations including those in the EGFR, KRAS, BRAF, and ERBB2 gene, or EML4-ALK gene. The correlation of KIF5B-RET fusion gene with smoking is still ambiguous [5]
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