title: Simultaneous diagnostic platform of genotyping EGFR, KRAS, and ALK in 510 Korean patients with non-small-cell lung cancer highlights significantly higher ALK rearrangement rate in advanced stage.
abstract: BACKGROUND
  Simultaneous genotyping has advantages in turnaround time and detecting the real mutational prevalence in unresectable non-small-cell lung cancer (NSCLC), a group not previously genetically characterized.
  
  
  METHODS
  We developed simultaneous panel of screening EGFR and KRAS mutations by direct sequencing or PNA clamping, and ALK rearrangement by fluorescent in situ hybridization (FISH) in multicenter manner.
  
  
  RESULTS
  Of 510 NSCLC Korean patients, simultaneous genotyping identified mutations of EGFR (29.0%) and KRAS (8.6%) and rearrangement of ALK (9.2%). Seven patients had overlaps in mutations. Although several well-known associations between genotypes and clinical characteristics were identified, we found no relationship between ALK rearrangement and sex or smoking history. Unlike the other genotype mutations, ALK rearrangement was associated with advanced disease. Among the ALK-negative group, patients with 10-15% of ALK FISH split shared characteristics, such as younger age and advanced stage disease, more with the ALK-positive group (>15% ALK FISH split) than <10% ALK FISH split group.
  
  
  CONCLUSIONS
  Simultaneous panel genotyping revealed more prevalent ALK rearrangements than reported in previous studies and their strong association with advanced stage irrespective of sex or smoking history. ALK rearrangement seems to be a marker for aggressive tumor biology and should be assessed in advanced disease.
authors.affiliation: Department of Hospital Pathology, College of Medicine, Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Tae-Jung
authors.initials: TJ
authors.lastname: Kim
authors.forename: Chan Kwon
authors.initials: CK
authors.lastname: Park
authors.forename: Chang Dong
authors.initials: CD
authors.lastname: Yeo
authors.forename: Kihoon
authors.initials: K
authors.lastname: Park
authors.forename: Chin Kook
authors.initials: CK
authors.lastname: Rhee
authors.forename: Jusang
authors.initials: J
authors.lastname: Kim
authors.forename: Seung Joon
authors.initials: SJ
authors.lastname: Kim
authors.forename: Sang Haak
authors.initials: SH
authors.lastname: Lee
authors.forename: Kyo-Young
authors.initials: KY
authors.lastname: Lee
authors.forename: Hyoung-Kyu
authors.initials: HK
authors.lastname: Yoon
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000077548:Anaplastic Lymphoma Kinase; D044466:Asian People / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D015321:Gene Rearrangement; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D056910:Republic of Korea; D012737:Sex Factors; D012907:Smoking / Q000453:epidemiology; D055815:Young Adult; D018631:ras Proteins / Q000235:genetics*
chemical_list: C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; C512478:EGFR protein, human; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins
keywords: ALK; EGFR; KRAS; fluorescence in situ hybridization; mutation; non-small-cell lung carcinoma