https://scholars.lib.ntu.edu.tw/handle/123456789/597085
標題: | Clinical mutational profiling of 1006 lung cancers by next generation sequencing | 作者: | Illei P.B. Belchis D. LI-HUI TSENG Nguyen D. De Marchi F. Haley L. Riel S. Beierl K. Zheng G. Brahmer J.R. Askin F.B. Gocke C.D. Eshleman J.R. Forde P.M. Lin M.-T. |
關鍵字: | Cancer; Lung; Mutation; Profiling; Sequencing | 公開日期: | 2017 | 出版社: | Impact Journals LLC | 卷: | 8 | 期: | 57 | 起(迄)頁: | 96684-96696 | 來源出版物: | Oncotarget | 摘要: | Analysis of lung adenocarcinomas for actionable mutations has become standard of care. Here, we report our experience using next generation sequencing (NGS) to examine AKT1, BRAF, EGFR, ERBB2, KRAS, NRAS, and PIK3CA genes in 1006 non-small cell lung cancers in a clinical diagnostic setting. NGS demonstrated high sensitivity. Among 760 mutations detected, the variant allele frequency (VAF) was 2-5% in 33 (4.3%) mutations and 2-10% in 101 (13%) mutations. A single bioinformatics pipeline using Torrent Variant Caller, however, missed a variety of EGFR mutations. Mutations were detected in KRAS (36% of tumors), EGFR (19%) including 8 (0.8%) within the extracellular domain (4 at codons 108 and 4 at codon 289), BRAF (6.3%), and PIK3CA (3.7%). With a broader reportable range, exon 19 deletion and p.L858R accounted for only 36% and 26% of EGFR mutations and p.V600E accounted for only 24% of BRAF mutations. NGS provided accurate sequencing of complex mutations seen in 19% of EGFR exon 19 deletion mutations. Doublet (compound) EGFR mutations were observed in 29 (16%) of 187 EGFR-mutated tumors, including 69% with two non-p. L858R missense mutations and 24% with p.L858 and non-p.L858R missense mutations. Concordant VAFs suggests doublet EGFR mutations were present in a dominant clone and cooperated in oncogenesis. Mutants with predicted impaired kinase, observed in 25% of BRAF-mutated tumors, were associated with a higher incidence of concomitant activating KRAS mutations. NGS demonstrates high analytic sensitivity, broad reportable range, quantitative VAF measurement, single molecule sequencing to resolve complex deletion mutations, and simultaneous detection of concomitant mutations. ? Illei et al. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85033779360&doi=10.18632%2foncotarget.18042&partnerID=40&md5=e29241c83be6bc53da561fe02174581b https://scholars.lib.ntu.edu.tw/handle/123456789/597085 |
ISSN: | 1949-2553 | DOI: | 10.18632/oncotarget.18042 | SDG/關鍵字: | B Raf kinase; epidermal growth factor receptor; epidermal growth factor receptor 2; K ras protein; mammalian target of rapamycin; mitogen activated protein kinase; AKT1 gene; Article; BRAF gene; controlled study; EGFR gene; ERBB2 gene; exon; gene; gene deletion; gene duplication; gene frequency; gene mutation; human; human tissue; lung cancer; major clinical study; missense mutation; mutational analysis; next generation sequencing; non small cell lung cancer; oncogene K ras; oncogene N ras; PIK3CA gene |
顯示於: | 基因體暨蛋白體醫學研究所 |
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