J Thorac Oncol. 2014 Mar;9(3):419-22. doi: 10.1097/JTO.0000000000000061.

HIP1-ALK, a Novel Fusion Protein Identified in Lung Adenocarcinoma.

Hong M, Kim RN, Song JY, Choi SJ, Oh E, Lira ME, Mao M, Takeuchi K, Han J, Kim J, Choi YL.

Author information

Departments of *Pathology, §Thoracic Surgery, Samsung Medical Center, Sungkyunkwan University College of Medicine, Seoul, Korea; †Department of Pharmacy, College of Pharmacy, Seoul National University, Seoul, Korea; ‡Laboratory of Cancer Genomics and Molecular Pathology, Samsung Biomedical Research Institute, Samsung Medical Center, Seoul, Korea; ‖Pfizer Oncology, San Diego, California; ¶Pathology Project for MolecularTargets of the Cancer Institute/Division of Pathology of the Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan; and #Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University School of Medicine, Seoul, Korea.

Abstract

INTRODUCTION:

The most common mechanism underlying overexpression and activation of anaplastic lymphoma kinase (ALK) in non-small-celllung carcinoma could be attributed to the formation of a fusion protein. To date, five fusion partners of ALK have been reported, namely, echinoderm microtubule associated protein like 4, tropomyosin-related kinase-fused gene, kinesin family member 5B, kinesin light chain 1, and protein tyrosine phosphatase, nonreceptor type 3.

METHODS:

In this article, we report a novel fusion gene huntingtin interacting protein 1 (HIP1)-ALK, which is conjoined between the huntingtin-interacting protein 1 gene HIP1 and ALK. Reverse-transcriptase polymerase chain reaction and immunohistochemical analysis were used to detect this fusion gene's transcript and protein expression, respectively. We had amplified the full-length cDNA sequence of this novel fusion gene by using 5'-rapid amplification of cDNA ends. The causative genomic translocation t(2;7)(p23;q11.23) for generating this novel fusion gene was verified by using genomic sequencing.

RESULTS:

The examined adenocarcinoma showed predominant acinar pattern, and ALK immunostaining was localized to the cytoplasm, with intense staining in the submembrane region. In break-apart, fluorescence in situ hybridization analysis for ALK, split of the 5' and 3' probe signals, and isolated 3' signals were observed. Reverse-transcriptase polymerase chain reaction revealed that the tumor harbored a novel fusion transcript in which exon 21 of HIP1 was fused to exon 20 of ALK in-frame.

CONCLUSION:

The novel fusion gene and its protein HIP1-ALK harboring epsin N-terminal homology, coiled-coil, juxtamembrane, and kinase domains, which could play a role in carcinogenesis, could become diagnostic and therapeutic target of the lung adenocarcinoma and deserve a further study in the future.