title: ALK, ROS1 and RET rearrangements in lung squamous cell carcinoma are very rare.
abstract: OBJECTIVE
  Chromosomal rearrangements of ALK and ROS1 genes in non-small cell lung carcinoma (NSCLC) define a molecular subgroup of lung adenocarcinoma (ADC) that is amenable to targeted therapy with tyrosine kinase inhibitors (TKIs) crizotinib. Emerging clinical studies have demonstrated that patients with RET-rearranged NSCLC may also benefit from existing RET TKIs, including cabozantinib and vandetanib. However, the reported cases of lung squamous cell carcinomas (SCC) harboring gene rearrangements have been detected via fluorescence in situ hybridization (FISH) or immunohistochemistry (IHC) from materials such as biopsy or resection. Fusion events identified in lung SCC raise the question of whether this histologic subtype should also be evaluated for merit molecular testing. This work was undertaken to study the prevalence of lung SCC harboring ALK, ROS1, and RET translocations.
  
  
  METHODS
  Squamous cell carcinomas were confirmed using both histological examination by pathologists and immunohistochemistry analysis with positive staining of P63 and CK5/6 combined with negative CK7 and TTF-1 staining. 214 samples from surgically resected patient tissues were used to search for ALK, ROS1, and RET rearrangements by a NanoString analysis method. Fusion events were detected in a single-tube, multiplex assay system that relied on a complementary strategy of interrogation of 3' gene overexpression and detection of specific fusion transcript variants.
  
  
  CONCLUSIONS
  ALK, ROS1 or RET gene rearrangements appeared 0 times out of 214 cases of lung SCC. Our data revealed that these fusions may be very rare in lung squamous cancer. The molecular screening strategy should therefore be focused on lung adenocarcinoma as the current National Comprehensive Cancer Network (NCCN) guideline recommends.
authors.affiliation: Translational Bioscience and Diagnostics, WuXi AppTec, Shanghai, China.
authors.forename: Weijie
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea.
authors.forename: Yoon-La
authors.initials: YL
authors.lastname: Choi
authors.affiliation: Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Song
authors.affiliation: Department of Pathology, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou University of Chinese Medicine, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, China.
authors.forename: Yazhen
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Translational Bioscience and Diagnostics, WuXi AppTec, Shanghai, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Translational Bioscience and Diagnostics, WuXi AppTec, Shanghai, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Translational Bioscience and Diagnostics, WuXi AppTec, Shanghai, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Translational Bioscience and Diagnostics, WuXi AppTec, Shanghai, China.
authors.forename: Ju
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Department of Pathology, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou University of Chinese Medicine, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, China. Electronic address: zhengguangjuan@163.com.
authors.forename: Guangjuan
authors.initials: G
authors.lastname: Zheng
authors.affiliation: Translational Bioscience and Diagnostics, WuXi AppTec, Shanghai, China. Electronic address: mao_m@yahoo.com.
authors.forename: Mao
authors.initials: M
authors.lastname: Mao
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077548:Anaplastic Lymphoma Kinase; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D015514:Oncogene Proteins, Fusion; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D014158:Transcription, Genetic; D014178:Translocation, Genetic
chemical_list: D015514:Oncogene Proteins, Fusion; D011518:Proto-Oncogene Proteins; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D011505:Protein-Tyrosine Kinases; D051096:Proto-Oncogene Proteins c-ret; C062333:ROS1 protein, human; D020794:Receptor Protein-Tyrosine Kinases
keywords: Anaplastic lymphoma kinase; Fusion; Squamous cell carcinoma