title: Molecular profiling of small cell lung cancer in a Japanese cohort.
abstract: OBJECTIVE
  Advances in the molecular profiling of lung adenocarcinoma over the past decade have led to a paradigm shift in its diagnosis and treatment. However, there are very few reports on the molecular profiles of small cell lung cancers (SCLCs). We therefore conducted the present Shizuoka Lung Cancer Mutation Study to analyze genomic aberrations in patients with thoracic malignancies.
  
  
  METHODS
  We collected samples of SCLC from a biobank system and analyzed their molecular profiles. We assessed 23 mutations in nine genes (EGFR, KRAS, BRAF, PIK3CA, NRAS, MEK1, AKT1, PTEN, and HER2) using pyrosequencing plus capillary electrophoresis. We also amplified EGFR, MET, PIK3CA, FGFR1, and FGFR2 using quantitative real-time polymerase chain reaction (PCR) and the fusion genes ALK, ROS1, and RET using reverse transcription PCR.
  
  
  RESULTS
  Between July 2011 and January 2013, 60 SCLC patients were enrolled in the study. Samples included eight surgically resected snap-frozen samples, 50 formalin-fixed paraffin-embedded samples, and seven pleural effusion samples. We detected 13 genomic aberrations in nine cases (15%), including an EGFR mutation (n=1, G719A), a KRAS mutation (n=1, G12D), PIK3CA mutations (n=3, E542K, E545K, E545Q), an AKT1 mutation (n=1, E17K), a MET amplification (n=1), and PIK3CA amplifications (n=6). EGFR and KRAS mutations were found in patients with combined SCLC and adenocarcinoma. No significant differences were detected in the characteristics of patients with and without genomic aberrations. However, serum neuron-specific enolase and progastrin-releasing peptide levels were significantly higher in patients without genomic aberrations than in those with aberrations (p=0.01 and 0.04, respectively).
  
  
  CONCLUSIONS
  Genomic aberrations were found in 15% SCLC patients, with PIK3CA amplifications most frequently observed. To further our understanding of the molecular profiles of SCLC, comprehensive mutational analyses should be conducted using massive parallel sequencing.
authors.affiliation: Division of Thoracic Oncology, Shizuoka Cancer Center, Nagaizumi-cho, Suntou-gun, Shizuoka, Japan; Division of Drug Discovery and Development, Shizuoka Cancer Center Research Institute, Nagaizumi-cho, Suntou-gun, Shizuoka, Japan.
authors.forename: Kazushige
authors.initials: K
authors.lastname: Wakuda
authors.affiliation: Division of Thoracic Oncology, Shizuoka Cancer Center, Nagaizumi-cho, Suntou-gun, Shizuoka, Japan; Division of Drug Discovery and Development, Shizuoka Cancer Center Research Institute, Nagaizumi-cho, Suntou-gun, Shizuoka, Japan. Electronic address: h.kenmotsu@scchr.jp.
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Kenmotsu
authors.affiliation: Division of Drug Discovery and Development, Shizuoka Cancer Center Research Institute, Nagaizumi-cho, Suntou-gun, Shizuoka, Japan.
authors.forename: Masakuni
authors.initials: M
authors.lastname: Serizawa
authors.affiliation: Division of Drug Discovery and Development, Shizuoka Cancer Center Research Institute, Nagaizumi-cho, Suntou-gun, Shizuoka, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Koh
authors.affiliation: Division of Thoracic Surgery, Shizuoka Cancer Center, Nagaizumi-cho, Suntou-gun, Shizuoka, Japan.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Isaka
authors.affiliation: Division of Thoracic Surgery, Shizuoka Cancer Center, Nagaizumi-cho, Suntou-gun, Shizuoka, Japan.
authors.forename: Shoji
authors.initials: S
authors.lastname: Takahashi
authors.affiliation: Division of Thoracic Oncology, Shizuoka Cancer Center, Nagaizumi-cho, Suntou-gun, Shizuoka, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Ono
authors.affiliation: Division of Thoracic Oncology, Shizuoka Cancer Center, Nagaizumi-cho, Suntou-gun, Shizuoka, Japan.
authors.forename: Tetsuhiko
authors.initials: T
authors.lastname: Taira
authors.affiliation: Division of Thoracic Oncology, Shizuoka Cancer Center, Nagaizumi-cho, Suntou-gun, Shizuoka, Japan.
authors.forename: Tateaki
authors.initials: T
authors.lastname: Naito
authors.affiliation: Division of Thoracic Oncology, Shizuoka Cancer Center, Nagaizumi-cho, Suntou-gun, Shizuoka, Japan.
authors.forename: Haruyasu
authors.initials: H
authors.lastname: Murakami
authors.affiliation: Clinical Trial Coordination Office, Shizuoka Cancer Center, Nagaizumi-cho, Suntou-gun, Shizuoka, Japan.
authors.forename: Keita
authors.initials: K
authors.lastname: Mori
authors.affiliation: Division of Diagnostic Radiology, Shizuoka Cancer Center, Nagaizumi-cho, Suntou-gun, Shizuoka, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Endo
authors.affiliation: Division of Pathology, Shizuoka Cancer Center, Nagaizumi-cho, Suntou-gun, Shizuoka, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakajima
authors.affiliation: Division of Thoracic Surgery, Shizuoka Cancer Center, Nagaizumi-cho, Suntou-gun, Shizuoka, Japan.
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Ohde
authors.affiliation: Division of Thoracic Oncology, Shizuoka Cancer Center, Nagaizumi-cho, Suntou-gun, Shizuoka, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Takahashi
authors.affiliation: Division of Thoracic Oncology, Shizuoka Cancer Center, Nagaizumi-cho, Suntou-gun, Shizuoka, Japan; Third Department of Internal Medicine, Wakayama Medical University, Kimiidera, Wakayama, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Yamamoto
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D007564:Japan; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D009363:Neoplasm Proteins / Q000235:genetics; D055752:Small Cell Lung Carcinoma / Q000235:genetics*
chemical_list: D009363:Neoplasm Proteins
keywords: Driver mutation; EGFR; Genomic aberration; Molecular profiling; PIK3CA; Small cell lung cancer