title: ALK gene amplification is associated with poor prognosis in colorectal carcinoma.
abstract: BACKGROUND
  Recently, the anaplastic lymphoma kinase (ALK) has been found to be altered in several solid and haematological tumours. ALK gene copy number changes and mutations in colorectal cancers (CRCs) are not well characterised. We aimed to study the prevalence of ALK copy number changes, translocations, gene mutations and protein expression in 770 CRC patients, and correlate these findings with molecular and clinico-pathological data.
  
  
  METHODS
  ALK gene copy number variations and ALK expression were evaluated by fluorescence in situ hybridisation (FISH) and immunohistochemistry, respectively.
  
  
  RESULTS
  Translocations of the ALK gene were not observed; 3.4% (26 out of 756) of the CRC patients tested had an increase in ALK gene copy number either amplification or gain. Interestingly, increased ALK gene copy number alteration was associated with poor prognosis (P=0.0135) and was an independent prognostic marker in multivariate Cox proportional hazards model. The study reveals a significant impact of ALK gene copy number alterations on the outcome of patients with CRC.
  
  
  CONCLUSIONS
  The findings of our study highlight a potential role of targeting ALK in advanced CRCs by using ALK FISH and ALK IHC as a screening tool to detect ALK alterations. Based on these findings, a potential role of ALK inhibitor as a therapeutic agent in a subset of CRC merits further investigation.
authors.affiliation: Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia.
authors.forename: P
authors.initials: P
authors.lastname: Bavi
authors.forename: Z
authors.initials: Z
authors.lastname: Jehan
authors.forename: R
authors.initials: R
authors.lastname: Bu
authors.forename: S
authors.initials: S
authors.lastname: Prabhakaran
authors.forename: N
authors.initials: N
authors.lastname: Al-Sanea
authors.forename: F
authors.initials: F
authors.lastname: Al-Dayel
authors.forename: M
authors.initials: M
authors.lastname: Al-Assiri
authors.forename: T
authors.initials: T
authors.lastname: Al-Halouly
authors.forename: R
authors.initials: R
authors.lastname: Sairafi
authors.forename: S
authors.initials: S
authors.lastname: Uddin
authors.forename: K S
authors.initials: KS
authors.lastname: Al-Kuraya
mesh_terms: D000368:Aged; D000077548:Anaplastic Lymphoma Kinase; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality; D005260:Female; D005784:Gene Amplification; D018628:Gene Dosage; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases