Cancer Res Treat.  2016 Jan;48(1):398-402. 10.4143/crt.2014.254.

SEC31A-ALK Fusion Gene in Lung Adenocarcinoma

• Kim RN
• Choi YL
• Lee MS
• Lira ME
• Mao M
• Mann D
• Stahl J
• Licon A
• Choi SJ
• Vrancken M
• Han J
• Wlodarska
• Kim J

• KMID: 2152299
• DOI: http://doi.org/10.4143/crt.2014.254

Abstract

Anaplastic lymphoma kinase (ALK) fusion is a common mechanism underlying pathogenesis of non-small cell lung carcinoma (NSCLC) where these rearrangements represent important diagnostic and therapeutic targets. In this study, we found a new ALK fusion gene, SEC31A-ALK, in lung carcinoma from a 53-year-old Korean man. The conjoined region in the fusion transcript was generated by the fusion of SEC31A exon 21 and ALK exon 20 by genomic rearrangement, which contributed to generation of an intact, in-frame open reading frame. SEC31A-ALK encodes a predicted fusion protein of 1,438 amino acids comprising the WD40 domain of SEC31A at the N-terminus and ALK kinase domain at the C-terminus. Fluorescence in situ hybridization studies suggested that SEC31A-ALK was generated by an unbalanced genomic rearrangement associated with loss of the 3'-end of SEC31A. This is the first report of SEC31A-ALK fusion transcript in clinical NSCLC, which could be a novel diagnostic and therapeutic target for patients with NSCLC.

Keyword

Lung neoplasms; Anaplastic lymphoma kinase; SEC31A; Genetic translocation

MeSH Terms

Adenocarcinoma*
Amino Acids
Exons
Fluorescence
Humans
In Situ Hybridization
Lung Neoplasms
Lung*
Lymphoma
Middle Aged
Open Reading Frames
Phosphotransferases
Translocation, Genetic
Amino Acids
Phosphotransferases

Figure

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  Fig. 1. (A) Computed tomography scan of the chest showing a solid nodule with a speculated margin (arrow) measuring 1.5-cm in size in the lower lobe of the right lung. (B) Anaplastic lymphoma kinase (ALK) immunohistochemical staining showing cytoplasmic staining of tumor cells (×100). (C) Fluorescence in situ hybridization assay of ALK showing ALK genomic rearrangement by split 5'- and 3'-probe signals (arrows). (D-F) Hematoxylin and eosin staining showing adenocarcinoma (D, ×100), and a mixture of acinar pattern (E, ×200) and solid pattern (F, ×200).

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  Fig. 2. Schematic (A) showing the intron containing and surrounding the conjoined region for genomic rearrangement for the SEC31A-ALK fusion gene encoding the fusion protein (B) harboring the WD and tyrosine kinase functional domains as well as the adjacent exons. (C, D) DNA sequence chromatograms showing the conjoined regions at the genomic DNA sequence level (C) and cDNA sequence level (D) of the SEC31A-ALK fusion gene.

Reference

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