Prospective genetic profiling of squamous cell lung cancer and adenosquamous carcinoma in Japanese patients by multitarget assays

BMC Cancer

Nobuyuki Yamamoto⁶  Yasuhisa Ohde⁵  Takashi Nakajima²  Isamu Hayashi²  Masato Abe²  Masahiro Endo⁴  Keita Mori¹  Shoji Takahashi⁵  Tomohiro Maniwa⁵  Akira Ono⁷  Tetsuhiko Taira⁷  Toshiaki Takahashi⁷  Mitsuhiro Isaka⁵  Yasuhiro Koh³  Masakuni Serizawa³  Hirotsugu Kenmotsu³ 

[1]Clinical Trial Coordination Office, Shizuoka Cancer Center, Nagaizumi-cho, Sunto-gun, Japan

[2]Division of Pathology, Shizuoka Cancer Center, Nagaizumi-cho, Sunto-gun, Japan

[3]Division of Drug Discovery and Development, Shizuoka Cancer Center Research Institute, Nagaizumi-cho, Sunto-gun, Japan

[4]Division of Diagnostic Radiology, Shizuoka Cancer Center, Nagaizumi-cho, Sunto-gun, Japan

[5]Division of Thoracic Surgery, Shizuoka Cancer Center, Nagaizumi-cho, Sunto-gun, Japan

[6]Third Department of Internal Medicine, Wakayama Medical University, Kimiidera, Wakayama, Japan

[7]Division of Thoracic Oncology, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka 411-8777, Japan

关键词: FGFR1 copy number gain;    PIK3CA mutation;    Driver mutation;    Genetic profiling;    Adenosquamos carcinoma;    Squamous cell carcinoma;    Lung cancer;   

Others  :  1120952
DOI  :  10.1186/1471-2407-14-786

 received in 2014-02-26, accepted in 2014-10-09,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 Kenmotsu et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

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