title: Prospective genetic profiling of squamous cell lung cancer and adenosquamous carcinoma in Japanese patients by multitarget assays.
abstract: BACKGROUND
  Despite considerable recent progress in the treatment of lung adenocarcinoma, there has been little progress in the development of efficacious molecular targeted therapies for squamous cell lung cancer. In addition to the recent comprehensive genome-wide characterization of squamous cell lung cancer, it is also important to genotype this form of cancer. We therefore conducted the Shizuoka Lung Cancer Mutation Study to analyze driver mutations in patients with thoracic malignancies. Here we report the results of genotyping in patients with squamous cell lung cancer.
  
  
  METHODS
  Based on the biobanking system, in conjunction with the clinic and pathology lab, we developed a genotyping panel designed to assess 24 mutations in 10 genes (EGFR, KRAS, BRAF, PIK3CA, NRAS, MEK1, AKT1, PTEN, HER2 and DDR2), EGFR, MET, PIK3CA, FGFR1 and FGFR2 copy numbers, and EML4-ALK and ROS1 translocations, using pyrosequencing plus capillary electrophoresis, quantitative polymerase chain reaction (PCR) and reverse-transcription PCR, respectively.
  
  
  RESULTS
  A total of 129 patients with squamous cell lung cancer and adenosquamous carcinoma were enrolled in this study between July 2011 and November 2012. We detected genetic alterations in 40% of all cases. Gene alterations included: EGFR mutations, 6%; KRAS mutations, 4%; PIK3CA mutations, 13%; NRAS mutations, 1%; KIF5b-RET fusion gene, 1%; EGFR copy number gain, 5%; PIK3CA copy number gain, 15%; and FGFR1 copy number gain, 5%. Twelve patients (9%) harbored simultaneous genetic alterations. Genetic alterations were detected more frequently in surgically-resected, snap-frozen samples than in formalin-fixed, paraffin-embedded samples (50% vs. 29%). In addition, patients aged ≤70 years old and never-smokers showed high frequencies of genetic alterations.
  
  
  CONCLUSIONS
  This study represents one of the largest prospective tumor-genotyping studies to be performed in Asian patients with squamous cell lung cancer. These results suggest that incorporation of genetic profiling into lung cancer clinical practice may facilitate the administration of personalized cancer treatments in patients with squamous cell lung cancer.
authors.affiliation: Division of Thoracic Oncology, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka 411-8777, Japan. h.kenmotsu@scchr.jp.
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Kenmotsu
authors.forename: Masakuni
authors.initials: M
authors.lastname: Serizawa
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Koh
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Isaka
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Takahashi
authors.forename: Tetsuhiko
authors.initials: T
authors.lastname: Taira
authors.forename: Akira
authors.initials: A
authors.lastname: Ono
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Maniwa
authors.forename: Shoji
authors.initials: S
authors.lastname: Takahashi
authors.forename: Keita
authors.initials: K
authors.lastname: Mori
authors.forename: Masahiro
authors.initials: M
authors.lastname: Endo
authors.forename: Masato
authors.initials: M
authors.lastname: Abe
authors.forename: Isamu
authors.initials: I
authors.lastname: Hayashi
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakajima
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Ohde
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Yamamoto
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People; D018070:Biological Specimen Banks; D018196:Carcinoma, Adenosquamous / Q000235:genetics* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D056915:DNA Copy Number Variations; D005260:Female; D020869:Gene Expression Profiling; D060005:Genotyping Techniques; D006801:Humans; D007564:Japan; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011446:Prospective Studies; D012307:Risk Factors