title: KLC1-ALK: a novel fusion in lung cancer identified using a formalin-fixed paraffin-embedded tissue only.
abstract: The promising results of anaplastic lymphoma kinase (ALK) inhibitors have changed the significance of ALK fusions in several types of cancer. These fusions are no longer mere research targets or diagnostic markers, but they are now directly linked to the therapeutic benefit of patients. However, most available tumor tissues in clinical settings are formalin-fixed and paraffin-embedded (FFPE), and this significantly limits detailed genetic studies in many clinical cases. Although recent technical improvements have allowed the analysis of some known mutations in FFPE tissues, identifying unknown fusion genes by using only FFPE tissues remains difficult. We developed a 5'-rapid amplification of cDNA ends-based system optimized for FFPE tissues and evaluated this system on a lung cancer tissue with ALK rearrangement and without the 2 known ALK fusions EML4-ALK and KIF5B-ALK. With this system, we successfully identified a novel ALK fusion, KLC1-ALK. The result was confirmed by reverse transcription-polymerase chain reaction and fluorescence in situ hybridization. Then, we synthesized the putative full-length cDNA of KLC1-ALK and demonstrated the transforming potential of the fusion kinase with assays using mouse 3T3 cells. To the best of our knowledge, KLC1-ALK is the first novel oncogenic fusion identified using only FFPE tissues. This finding will broaden the potential value of archival FFPE tissues and provide further biological and clinical insights into ALK-positive lung cancer.
authors.affiliation: Pathology Project for Molecular Targets, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Togashi
authors.forename: Manabu
authors.initials: M
authors.lastname: Soda
authors.forename: Seiji
authors.initials: S
authors.lastname: Sakata
authors.forename: Emiko
authors.initials: E
authors.lastname: Sugawara
authors.forename: Satoko
authors.initials: S
authors.lastname: Hatano
authors.forename: Reimi
authors.initials: R
authors.lastname: Asaka
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakajima
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Mano
authors.forename: Kengo
authors.initials: K
authors.lastname: Takeuchi
mesh_terms: D016475:3T3 Cells; D000077548:Anaplastic Lymphoma Kinase; D000818:Animals; D015321:Gene Rearrangement; D016547:Kinesins; D008175:Lung Neoplasms / Q000235:genetics*; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000032:analysis / Q000235:genetics*; D016612:Paraffin Embedding; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C000715695:Kns2 protein, mouse; D008869:Microtubule-Associated Proteins; D015514:Oncogene Proteins, Fusion; C000626174:Alk protein, mouse; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases; D016547:Kinesins