https://scholars.lib.ntu.edu.tw/handle/123456789/597095
標題: | Clinical detection and categorization of uncommon and concomitant mutations involving BRAF | 作者: | Zheng G. LI-HUI TSENG Chen G. Haley L. Illei P. Gocke C.D. Eshleman J.R. Lin M.-T. |
關鍵字: | BRAF; Colorectal cancer; Concomitant mutation; Kinase activity; Lung cancer; Melanoma; Next generation sequencing | 公開日期: | 2015 | 出版社: | BioMed Central Ltd. | 卷: | 15 | 期: | 1 | 來源出版物: | BMC Cancer | 摘要: | Background: Selective BRAF inhibitors, vemurafenib and dabrafenib, and the MEK inhibitor, trametinib, have been approved for treatment of metastatic melanomas with a BRAF p.V600E mutation. The clinical significance of non-codon 600 mutations remains unclear, in part, due to variation of kinase activity for different mutants. Methods: In this study, we categorized BRAF mutations according to the reported mutant kinase activity. A total of 1027 lung cancer, colorectal cancer or melanoma specimens were submitted for clinical mutation detection by next generation sequencing. Results: Non-codon 600 mutations were observed in 37 % of BRAF-mutated tumors. Of all BRAF mutants, 75 % were kinase-activated, 15 % kinase-impaired and 10 % kinase-unknown. The most common kinase-impaired mutant involves codon 594, specifically, p.D594G (c.1781A > G) and p.D594N (c.1780G > A). Lung cancers showed significantly higher incidences of kinase-impaired or kinase-unknown mutants. Kinase-impaired BRAF mutants showed a significant association with concomitant activating KRAS or NRAS mutations, but not PIK3CA mutations, supporting the reported interaction of these mutations. Conclusions:BRAF mutants with impaired or unknown kinase activity as well as concomitant kinase-impaired BRAF mutations and RAS mutations were detected in lung cancers, colorectal cancers and melanomas. Different therapeutic strategies based on the BRAF mutant kinase activity and the concomitant mutations may be worthwhile. ? 2015 Zheng et al. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84945120153&doi=10.1186%2fs12885-015-1811-y&partnerID=40&md5=d6858e36b448205ad70ea7c7e5a1fd1f https://scholars.lib.ntu.edu.tw/handle/123456789/597095 |
ISSN: | 1471-2407 | DOI: | 10.1186/s12885-015-1811-y | SDG/關鍵字: | phosphotransferase; protein serine threonine kinase; B Raf kinase; phosphotransferase; adult; aged; Article; BRAF gene; colorectal cancer; controlled study; enzyme activity; female; gene frequency; gene interaction; gene mutation; gene sequence; genetic analysis; genetic variability; heterozygosity; human; human tissue; limit of detection; lung cancer; major clinical study; male; melanoma; next generation sequencing; oncogene; oncogene N ras; protein phosphorylation; sequence alignment; signal transduction; single nucleotide polymorphism; somatic mutation; colorectal tumor; enzymology; genetics; high throughput sequencing; lung tumor; melanoma; metabolism; middle aged; mutation; single nucleotide polymorphism; very elderly; Adult; Aged; Aged, 80 and over; Colorectal Neoplasms; Female; High-Throughput Nucleotide Sequencing; Humans; Lung Neoplasms; Male; Melanoma; Middle Aged; Mutation; Phosphotransferases; Polymorphism, Single Nucleotide; Proto-Oncogene Proteins B-raf |
顯示於: | 基因體暨蛋白體醫學研究所 |
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