title: Anaplastic Lymphoma Kinase Rearrangement in Digestive Tract Cancer: Implication for Targeted Therapy in Chinese Population.
abstract: BACKGROUND
  Anaplastic lymphoma kinase (ALK) rearrangements define a subgroup of lung cancer which is eligible to targeted kinase inhibition. The aim of this study is to observe the incidence rate of ALK fusion in a large cohort of Chinese digestive tract cancer patients.
  
  
  METHODS
  Tissue microarray (TMA) was constructed from 808 digestive tract cancer cases, including 169 esophageal squamous cell carcinoma, 182 gastric cancer and 457 colorectal cancer (CRC) cases. We tested all cases for ALK expression via a fully automated immunohistochemistry (IHC) assay. The IHC-positive cases were subjected to fluorescence in situ hybridization (FISH), real-time polymerase chain reaction (qRT-PCR), target gene enrichment and sequencing for confirmation of ALK gene rearrangement and discovery of novel fusion partner.
  
  
  RESULTS
  Among the tested cases, 2 (0.44%) CRC cases showed positive both by IHC and FISH. By qRT-PCR, EML4-ALK fusion was found in one IHC-positive CRC case. In another IHC-positive CRC case, target gene enrichment and sequencing revealed ALK was fused to a novel partner, spectrin beta non-erythrocytic 1 (SPTBN1). One gastric cancer case showed partially positive IHC result, but no fusion was found by FISH and gene sequencing.
  
  
  CONCLUSIONS
  The incidence rate of ALK gene fusion in Chinese CRC patients was 0.44%,but not detectable in gastric and esophageal cancers. The novel SPTBN1 -ALK fusion, together with other ALK fusion genes, may become a potential target for anti-ALK therapy.
authors.affiliation: Department of Pathology, Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, PR China.
authors.forename: Jianming
authors.initials: J
authors.lastname: Ying
authors.affiliation: Department of Abdominal Surgical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, PR China.
authors.forename: Chen
authors.initials: C
authors.lastname: Lin
authors.affiliation: MyGenostics Inc., Baltimore, MD, United States of America.
authors.forename: Jian
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Pathology, Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Guo
authors.affiliation: Department of Pathology, Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, PR China.
authors.forename: Tian
authors.initials: T
authors.lastname: Qiu
authors.affiliation: Department of Pathology, Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, PR China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Ling
authors.affiliation: Department of Pathology, Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, PR China.
authors.forename: Ling
authors.initials: L
authors.lastname: Shan
authors.affiliation: Department of Abdominal Surgical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, PR China.
authors.forename: Haitao
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Department of Abdominal Surgical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, PR China.
authors.forename: Dongbing
authors.initials: D
authors.lastname: Zhao
authors.affiliation: Department of Abdominal Surgical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, PR China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Abdominal Surgical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, PR China.
authors.forename: Jianwei
authors.initials: J
authors.lastname: Liang
authors.affiliation: Department of Abdominal Surgical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, PR China.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Laboratory of Cell and Molecular Biology & State Key Laboratory of Molecular Oncology, Cancer Institute & Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, PR China.
authors.forename: Yuchen
authors.initials: Y
authors.lastname: Jiao
authors.affiliation: Department of Pathology, Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, PR China.
authors.forename: Ning
authors.initials: N
authors.lastname: Lu
authors.affiliation: Department of Abdominal Surgical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, PR China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhao
mesh_terms: D000328:Adult; D000368:Aged; D000077548:Anaplastic Lymphoma Kinase; D044466:Asian People / Q000235:genetics; D002681:China; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D004938:Esophageal Neoplasms / Q000201:enzymology / Q000235:genetics*; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D018307:Neoplasms, Squamous Cell / Q000201:enzymology / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D013274:Stomach Neoplasms / Q000201:enzymology / Q000235:genetics*; D052416:Targeted Gene Repair / Q000379:methods; D046888:Tissue Array Analysis; D055815:Young Adult
chemical_list: D004273:DNA, Neoplasm; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases