Kazushige Wakuda1, Hirotsugu Kenmotsu2, Masakuni Serizawa3, Yasuhiro Koh3, Mitsuhiro Isaka4, Shoji Takahashi4, Akira Ono5, Tetsuhiko Taira5, Tateaki Naito5, Haruyasu Murakami5, Keita Mori6, Masahiro Endo7, Takashi Nakajima8, Yasuhisa Ohde4, Toshiaki Takahashi5, Nobuyuki Yamamoto9. 1. 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. 2. 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. 3. Division of Drug Discovery and Development, Shizuoka Cancer Center Research Institute, Nagaizumi-cho, Suntou-gun, Shizuoka, Japan. 4. Division of Thoracic Surgery, Shizuoka Cancer Center, Nagaizumi-cho, Suntou-gun, Shizuoka, Japan. 5. Division of Thoracic Oncology, Shizuoka Cancer Center, Nagaizumi-cho, Suntou-gun, Shizuoka, Japan. 6. Clinical Trial Coordination Office, Shizuoka Cancer Center, Nagaizumi-cho, Suntou-gun, Shizuoka, Japan. 7. Division of Diagnostic Radiology, Shizuoka Cancer Center, Nagaizumi-cho, Suntou-gun, Shizuoka, Japan. 8. Division of Pathology, Shizuoka Cancer Center, Nagaizumi-cho, Suntou-gun, Shizuoka, Japan. 9. Division of Thoracic Oncology, Shizuoka Cancer Center, Nagaizumi-cho, Suntou-gun, Shizuoka, Japan; Third Department of Internal Medicine, Wakayama Medical University, Kimiidera, Wakayama, Japan.
Abstract
OBJECTIVES: 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. MATERIALS AND 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). CONCLUSION: 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.
OBJECTIVES: 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. MATERIALS AND 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 SCLCpatients 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). CONCLUSION: Genomic aberrations were found in 15% SCLCpatients, 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.
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