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

Kenmotsu H, Serizawa M, Koh Y, Isaka M, Takahashi T, Taira T, Ono A, Maniwa T, Takahashi S, Mori K, Endo M, Abe M, Hayashi I, Nakajima T, Ohde Y, Yamamoto N - BMC Cancer (2014)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Division of Thoracic Oncology, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka 411-8777, Japan. h.kenmotsu@scchr.jp.

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.

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Related in: MedlinePlus

Relative proportions of genetic alterations in squamous cell lung cancer and adenosquamous carcinoma (overall, n = 129). A: Pie chart shows relative proportions of genetic alterations. B: Bar chart shows relative proportions of genetic alterations. MUT: mutant, CNG: copy number gain.
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Fig1: Relative proportions of genetic alterations in squamous cell lung cancer and adenosquamous carcinoma (overall, n = 129). A: Pie chart shows relative proportions of genetic alterations. B: Bar chart shows relative proportions of genetic alterations. MUT: mutant, CNG: copy number gain.

Mentions: We detected genetic alterations in 40% of all cases. Figure 1 shows the frequencies of genetic alterations in patients with squamous cell lung cancer. The genetic alterations included: EGFR mutation in eight (6%); KRAS mutation in five (4%); PIK3CA mutation in 17 (13%); NRAS mutation in one (1%); KIF5b-RET fusion in one (1%); EGFR copy number gain in six (5%); PIK3CA copy number gain in 19 (15%); and FGFR1 copy number gain in six (5%) (Additional file 3: Table S2 and Additional file 4: Table S3). Of eight patients with EGFR mutation, four had the L858R point mutation in exon 21, and three had deletions in exon 19. In addition, the frequencies of genetic alterations in surgically-resected, snap-frozen samples and FFPE samples from patients with squamous cell lung cancer were analyzed (Figure 2), and the following alterations were detected: EGFR mutation in 8% and 5%, KRAS mutation in 3% and 5%, PIK3CA mutation in 17% and 9%, EGFR copy number gain in 8% and 2%, PIK3CA copy number gain in 19% and 11%, and FGFR1 copy number gain in 8% and 2%, respectively.Figure 1


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

Kenmotsu H, Serizawa M, Koh Y, Isaka M, Takahashi T, Taira T, Ono A, Maniwa T, Takahashi S, Mori K, Endo M, Abe M, Hayashi I, Nakajima T, Ohde Y, Yamamoto N - BMC Cancer (2014)

Relative proportions of genetic alterations in squamous cell lung cancer and adenosquamous carcinoma (overall, n = 129). A: Pie chart shows relative proportions of genetic alterations. B: Bar chart shows relative proportions of genetic alterations. MUT: mutant, CNG: copy number gain.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4221703&req=5

Fig1: Relative proportions of genetic alterations in squamous cell lung cancer and adenosquamous carcinoma (overall, n = 129). A: Pie chart shows relative proportions of genetic alterations. B: Bar chart shows relative proportions of genetic alterations. MUT: mutant, CNG: copy number gain.
Mentions: We detected genetic alterations in 40% of all cases. Figure 1 shows the frequencies of genetic alterations in patients with squamous cell lung cancer. The genetic alterations included: EGFR mutation in eight (6%); KRAS mutation in five (4%); PIK3CA mutation in 17 (13%); NRAS mutation in one (1%); KIF5b-RET fusion in one (1%); EGFR copy number gain in six (5%); PIK3CA copy number gain in 19 (15%); and FGFR1 copy number gain in six (5%) (Additional file 3: Table S2 and Additional file 4: Table S3). Of eight patients with EGFR mutation, four had the L858R point mutation in exon 21, and three had deletions in exon 19. In addition, the frequencies of genetic alterations in surgically-resected, snap-frozen samples and FFPE samples from patients with squamous cell lung cancer were analyzed (Figure 2), and the following alterations were detected: EGFR mutation in 8% and 5%, KRAS mutation in 3% and 5%, PIK3CA mutation in 17% and 9%, EGFR copy number gain in 8% and 2%, PIK3CA copy number gain in 19% and 11%, and FGFR1 copy number gain in 8% and 2%, respectively.Figure 1

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Division of Thoracic Oncology, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka 411-8777, Japan. h.kenmotsu@scchr.jp.

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.

Show MeSH
Related in: MedlinePlus