Mutation incidence and coincidence in non small-cell lung cancer: meta-analyses by ethnicity and histology (mutMap)

被引:523
作者
Dearden, S. [1 ]
Stevens, J. [1 ]
Wu, Y. -L. [2 ]
Blowers, D. [3 ]
机构
[1] AstraZeneca, Personalised Healthcare & Biomarkers, R&D Genet, Macclesfield SK10 4TG, Cheshire, England
[2] Guangdong Gen Hosp, Guangdong Lung Canc Inst, Guangzhou, Guangdong, Peoples R China
[3] AstraZeneca, Oncol iMed, Macclesfield SK10 4TG, Cheshire, England
关键词
geography; histology; lung cancer; mutation coincidence; oncogenes; GROWTH-FACTOR-RECEPTOR; SOMATIC MUTATIONS; ACQUIRED-RESISTANCE; 1ST-LINE TREATMENT; OPEN-LABEL; GEFITINIB; ADENOCARCINOMA; CHEMOTHERAPY; EGFR; AMPLIFICATION;
D O I
10.1093/annonc/mdt205
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Meta-analyses were conducted to characterize patterns of mutation incidence in non small-cell lung cancer (NSCLC). Nine genes with the most complete published mutation coincidence data were evaluated. One meta-analysis generated a 'mutMap' to visually represent mutation coincidence by ethnicity (Western/Asian) and histology (adenocarcinoma [ADC] or squamous cell carcinoma). Another meta-analysis evaluated incidence of individual mutations. Extended analyses explored incidence of EGFR and KRAS mutations by ethnicity, histology, and smoking status. Genes evaluated were TP53, EGFR, KRAS, LKB1, EML4-ALK, PTEN, BRAF, PIK3CA, and ErbB2. The mutMap highlighted mutation coincidences occurring in >= 5% of patients, including TP53 with KRAS or EGFR mutations in patients with ADC, and TP53 with LKB1 mutation in Western patients. TP53 was the most frequently mutated gene overall. Frequencies of TP53, EGFR, KRAS, LKB1, PTEN, and BRAF mutations were influenced by histology and/or ethnicity. Although EGFR mutations were most frequent in patients with ADC and never/light smokers from Asia, and KRAS mutations were most frequent in patients with ADC and ever/heavy smokers from Western countries, both were detected outside these subgroups. Potential molecular pathology segments of NSCLC were identified. Further studies of mutations in NSCLC are warranted to facilitate more specific diagnoses and guide treatment.
引用
收藏
页码:2371 / 2376
页数:6
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