Clinicopathological features of nonsmall cell lung carcinomas with BRAF mutations

T. Kinno, K. Tsuta, K. Shiraishi, T. Mizukami, M. Suzuki, A. Yoshida, K. Suzuki, Hisao Asamura, K. Furuta, T. Kohno, R. Kushima

Research output: Contribution to journalArticle

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Abstract

Background: Recently, driver tyrosine kinase gene mutations have been detected in malignant tumors, including lung tumors. Notwithstanding their attractiveness as targets for molecular therapy, limited information is available regarding BRAF-mutated lung carcinomas. Materials and methods: BRAF mutation status was determined in 2001 surgically resected nonsmall-cell lung cancer (NSCLC) cases using high-resolution melting analysis (HRMA) followed by Sanger sequencing and/or deep sequencing using next generation sequencer. Results: BRAF mutations were detected in 26 (1.3%) of 2001 NSCLC cases (25 adenocarcinomas and 1 squamous cell carcinoma). In the 26 cases, 13 mutation genotypes were identified, including V600E (8 of 26; 30.8%), G469A (6 of 26; 23.1%), K601E (4 of 26; 15.4%), and other residual mutations (1 of 26; 0.04%). Of the 13 genotypes, 4 genotypes (G464E, G596R, A598T, and G606R) had not been previously reported in lung cancer. The overall survival rate was not significantly different between patients with wild-type BRAF and those with V600E or non-V600E BRAF mutations (P=0.49 and P = 0.15, respectively). Histomorphological analysis revealed that focal clear cell changes were present in 75% of V600Emutated tumors. All V600E BRAF-mutated tumors were negative for other driver gene alterations including epidermal growth factor receptor (EGFR) and KRAS mutations and the anaplastic lymphoma kinase gene translocation, whereas five tumors with non-V600E BRAF mutations (four G469A and one G464E/G466R) showed concomitant EGFR mutations. Conclusion: The frequency of BRAF mutations in lung cancer was low in an Asian cohort. Furthermore, BRAF mutation status lacked prognostic significance in this patient population.

Original languageEnglish
Article numbermdt495
Pages (from-to)138-142
Number of pages5
JournalAnnals of Oncology
Volume25
Issue number1
DOIs
Publication statusPublished - 2014
Externally publishedYes

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Carcinoma
Lung
Mutation
Genotype
Neoplasms
Epidermal Growth Factor Receptor
Non-Small Cell Lung Carcinoma
Lung Neoplasms
Genes
High-Throughput Nucleotide Sequencing
Mutation Rate
Protein-Tyrosine Kinases
Freezing
Squamous Cell Carcinoma
Adenocarcinoma
Survival Rate
Population

Keywords

  • Asian
  • BRAF gene mutation
  • Lung carcinoma

ASJC Scopus subject areas

  • Oncology
  • Hematology

Cite this

Kinno, T., Tsuta, K., Shiraishi, K., Mizukami, T., Suzuki, M., Yoshida, A., ... Kushima, R. (2014). Clinicopathological features of nonsmall cell lung carcinomas with BRAF mutations. Annals of Oncology, 25(1), 138-142. [mdt495]. https://doi.org/10.1093/annonc/mdt495

Clinicopathological features of nonsmall cell lung carcinomas with BRAF mutations. / Kinno, T.; Tsuta, K.; Shiraishi, K.; Mizukami, T.; Suzuki, M.; Yoshida, A.; Suzuki, K.; Asamura, Hisao; Furuta, K.; Kohno, T.; Kushima, R.

In: Annals of Oncology, Vol. 25, No. 1, mdt495, 2014, p. 138-142.

Research output: Contribution to journalArticle

Kinno, T, Tsuta, K, Shiraishi, K, Mizukami, T, Suzuki, M, Yoshida, A, Suzuki, K, Asamura, H, Furuta, K, Kohno, T & Kushima, R 2014, 'Clinicopathological features of nonsmall cell lung carcinomas with BRAF mutations', Annals of Oncology, vol. 25, no. 1, mdt495, pp. 138-142. https://doi.org/10.1093/annonc/mdt495
Kinno T, Tsuta K, Shiraishi K, Mizukami T, Suzuki M, Yoshida A et al. Clinicopathological features of nonsmall cell lung carcinomas with BRAF mutations. Annals of Oncology. 2014;25(1):138-142. mdt495. https://doi.org/10.1093/annonc/mdt495
Kinno, T. ; Tsuta, K. ; Shiraishi, K. ; Mizukami, T. ; Suzuki, M. ; Yoshida, A. ; Suzuki, K. ; Asamura, Hisao ; Furuta, K. ; Kohno, T. ; Kushima, R. / Clinicopathological features of nonsmall cell lung carcinomas with BRAF mutations. In: Annals of Oncology. 2014 ; Vol. 25, No. 1. pp. 138-142.
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abstract = "Background: Recently, driver tyrosine kinase gene mutations have been detected in malignant tumors, including lung tumors. Notwithstanding their attractiveness as targets for molecular therapy, limited information is available regarding BRAF-mutated lung carcinomas. Materials and methods: BRAF mutation status was determined in 2001 surgically resected nonsmall-cell lung cancer (NSCLC) cases using high-resolution melting analysis (HRMA) followed by Sanger sequencing and/or deep sequencing using next generation sequencer. Results: BRAF mutations were detected in 26 (1.3{\%}) of 2001 NSCLC cases (25 adenocarcinomas and 1 squamous cell carcinoma). In the 26 cases, 13 mutation genotypes were identified, including V600E (8 of 26; 30.8{\%}), G469A (6 of 26; 23.1{\%}), K601E (4 of 26; 15.4{\%}), and other residual mutations (1 of 26; 0.04{\%}). Of the 13 genotypes, 4 genotypes (G464E, G596R, A598T, and G606R) had not been previously reported in lung cancer. The overall survival rate was not significantly different between patients with wild-type BRAF and those with V600E or non-V600E BRAF mutations (P=0.49 and P = 0.15, respectively). Histomorphological analysis revealed that focal clear cell changes were present in 75{\%} of V600Emutated tumors. All V600E BRAF-mutated tumors were negative for other driver gene alterations including epidermal growth factor receptor (EGFR) and KRAS mutations and the anaplastic lymphoma kinase gene translocation, whereas five tumors with non-V600E BRAF mutations (four G469A and one G464E/G466R) showed concomitant EGFR mutations. Conclusion: The frequency of BRAF mutations in lung cancer was low in an Asian cohort. Furthermore, BRAF mutation status lacked prognostic significance in this patient population.",
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T1 - Clinicopathological features of nonsmall cell lung carcinomas with BRAF mutations

AU - Kinno, T.

AU - Tsuta, K.

AU - Shiraishi, K.

AU - Mizukami, T.

AU - Suzuki, M.

AU - Yoshida, A.

AU - Suzuki, K.

AU - Asamura, Hisao

AU - Furuta, K.

AU - Kohno, T.

AU - Kushima, R.

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N2 - Background: Recently, driver tyrosine kinase gene mutations have been detected in malignant tumors, including lung tumors. Notwithstanding their attractiveness as targets for molecular therapy, limited information is available regarding BRAF-mutated lung carcinomas. Materials and methods: BRAF mutation status was determined in 2001 surgically resected nonsmall-cell lung cancer (NSCLC) cases using high-resolution melting analysis (HRMA) followed by Sanger sequencing and/or deep sequencing using next generation sequencer. Results: BRAF mutations were detected in 26 (1.3%) of 2001 NSCLC cases (25 adenocarcinomas and 1 squamous cell carcinoma). In the 26 cases, 13 mutation genotypes were identified, including V600E (8 of 26; 30.8%), G469A (6 of 26; 23.1%), K601E (4 of 26; 15.4%), and other residual mutations (1 of 26; 0.04%). Of the 13 genotypes, 4 genotypes (G464E, G596R, A598T, and G606R) had not been previously reported in lung cancer. The overall survival rate was not significantly different between patients with wild-type BRAF and those with V600E or non-V600E BRAF mutations (P=0.49 and P = 0.15, respectively). Histomorphological analysis revealed that focal clear cell changes were present in 75% of V600Emutated tumors. All V600E BRAF-mutated tumors were negative for other driver gene alterations including epidermal growth factor receptor (EGFR) and KRAS mutations and the anaplastic lymphoma kinase gene translocation, whereas five tumors with non-V600E BRAF mutations (four G469A and one G464E/G466R) showed concomitant EGFR mutations. Conclusion: The frequency of BRAF mutations in lung cancer was low in an Asian cohort. Furthermore, BRAF mutation status lacked prognostic significance in this patient population.

AB - Background: Recently, driver tyrosine kinase gene mutations have been detected in malignant tumors, including lung tumors. Notwithstanding their attractiveness as targets for molecular therapy, limited information is available regarding BRAF-mutated lung carcinomas. Materials and methods: BRAF mutation status was determined in 2001 surgically resected nonsmall-cell lung cancer (NSCLC) cases using high-resolution melting analysis (HRMA) followed by Sanger sequencing and/or deep sequencing using next generation sequencer. Results: BRAF mutations were detected in 26 (1.3%) of 2001 NSCLC cases (25 adenocarcinomas and 1 squamous cell carcinoma). In the 26 cases, 13 mutation genotypes were identified, including V600E (8 of 26; 30.8%), G469A (6 of 26; 23.1%), K601E (4 of 26; 15.4%), and other residual mutations (1 of 26; 0.04%). Of the 13 genotypes, 4 genotypes (G464E, G596R, A598T, and G606R) had not been previously reported in lung cancer. The overall survival rate was not significantly different between patients with wild-type BRAF and those with V600E or non-V600E BRAF mutations (P=0.49 and P = 0.15, respectively). Histomorphological analysis revealed that focal clear cell changes were present in 75% of V600Emutated tumors. All V600E BRAF-mutated tumors were negative for other driver gene alterations including epidermal growth factor receptor (EGFR) and KRAS mutations and the anaplastic lymphoma kinase gene translocation, whereas five tumors with non-V600E BRAF mutations (four G469A and one G464E/G466R) showed concomitant EGFR mutations. Conclusion: The frequency of BRAF mutations in lung cancer was low in an Asian cohort. Furthermore, BRAF mutation status lacked prognostic significance in this patient population.

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