Clinicopathologic features and outcomes of patients with lung adenocarcinomas harboring BRAF mutations in the Lung Cancer Mutation Consortium.
Abstract | BACKGROUND: METHODS: RESULTS: Twenty-one BRAF mutations were identified in 951 patients with adenocarcinomas (2.2%; 95% confidence interval [CI], 1.4%-3.4%): 17 (81%; 95% CI, 60%-92%) were BRAF(V600E) mutations, and 4 were non-BRAF(V600E) mutations. Among the 733 cases tested for all 10 genes, BRAF mutations were more likely to occur than most other genotypic abnormalities in current or former smokers (BRAF vs sensitizing EGFR, 82% vs 36%, mid-P < .001; BRAF vs ALK, 39%, mid-P = .003; BRAF vs other mutations, 49%, mid-P = .02; BRAF vs patients with more than 1 oncogenic driver [doubleton], 46%, mid-P = .04.) The double-mutation rate was 16% among patients with BRAF mutations but 5% among patients with other genomic abnormalities (mid-P = .045). Differences were not found in survival between patients with BRAF mutations and those with other genomic abnormalities (P > .20). CONCLUSIONS: BRAF mutations occurred in 2.2% of advanced-stage lung adenocarcinomas, were most commonly V600E, and were associated with distinct clinicopathologic features in comparison with other genomic subtypes and with a high mutation rate in more than 1 gene. These findings underscore the importance of comprehensive genomic profiling in assessing patients with advanced lung adenocarcinomas.
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Authors | Liza C Villaruz, Mark A Socinski, Shira Abberbock, Lynne D Berry, Bruce E Johnson, David J Kwiatkowski, A John Iafrate, Marileila Varella-Garcia, Wilbur A Franklin, D Ross Camidge, Lecia V Sequist, Eric B Haura, Mark Ladanyi, Brenda F Kurland, Kelly Kugler, John D Minna, Paul A Bunn, Mark G Kris |
Journal | Cancer
(Cancer)
Vol. 121
Issue 3
Pg. 448-56
(Feb 01 2015)
ISSN: 1097-0142 [Electronic] United States |
PMID | 25273224
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Copyright | © 2014 American Cancer Society. |
Chemical References |
- KRAS protein, human
- Proto-Oncogene Proteins
- Phosphatidylinositol 3-Kinases
- Class I Phosphatidylinositol 3-Kinases
- PIK3CA protein, human
- EGFR protein, human
- ERBB2 protein, human
- ErbB Receptors
- MET protein, human
- Proto-Oncogene Proteins c-met
- Receptor, ErbB-2
- AKT1 protein, human
- BRAF protein, human
- Proto-Oncogene Proteins B-raf
- Proto-Oncogene Proteins c-akt
- MAP Kinase Kinase 1
- MAP2K1 protein, human
- Proto-Oncogene Proteins p21(ras)
- ras Proteins
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Topics |
- Adenocarcinoma
(enzymology, genetics, pathology)
- Adenocarcinoma of Lung
- Adolescent
- Adult
- Aged
- Aged, 80 and over
- Class I Phosphatidylinositol 3-Kinases
- Cohort Studies
- ErbB Receptors
(genetics)
- Female
- Gene Amplification
- Humans
- Lung Neoplasms
(enzymology, genetics, pathology)
- MAP Kinase Kinase 1
(genetics)
- Male
- Middle Aged
- Mutation
- Phosphatidylinositol 3-Kinases
(genetics)
- Proto-Oncogene Proteins
(genetics)
- Proto-Oncogene Proteins B-raf
(genetics)
- Proto-Oncogene Proteins c-akt
(genetics)
- Proto-Oncogene Proteins c-met
(genetics)
- Proto-Oncogene Proteins p21(ras)
- Receptor, ErbB-2
(genetics)
- Young Adult
- ras Proteins
(genetics)
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