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首页> 外文期刊>Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer >Using whole genome amplification (WGA) of low-volume biopsies to assess the prognostic role of EGFR, KRAS, p53, and CMET mutations in advanced-stage non-small cell lung cancer (NSCLC).
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Using whole genome amplification (WGA) of low-volume biopsies to assess the prognostic role of EGFR, KRAS, p53, and CMET mutations in advanced-stage non-small cell lung cancer (NSCLC).

机译：使用小批量活检的全基因组扩增（WGA）评估EGFR，KRAS，p53和CMET突变在晚期非小细胞肺癌（NSCLC）中的预后作用。

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BACKGROUND: Progression of non-small cell lung cancer (NSCLC) from early- to late-stage may signify the accumulation of gene mutations. An advanced-stage tumor's mutation profile may also have prognostic value, guiding treatment decisions. Mutation detection of multiple genes is limited by the low amount of deoxyribonucleic acid extracted from low-volume diagnostic lung biopsies. We explored whole genome amplification (WGA) to enable multiple molecular analyses. METHODS: Eighty-eight advanced-stage NSCLC patients were enrolled. Their low-volume lung biopsies underwent WGA before direct sequencing for epidermal growth factor receptor (EGFR), KRAS (rat sarcoma virus), p53, and CMET (mesenchymal-epithelial transition factor) mutations. Overall survival impact was examined. Surgically-resected tumors from 133 early-stage NSCLC patients were sequenced for EGFR, KRAS and p53 mutations. We compared the mutation frequencies of both groups. RESULTS: It is feasible for low-volume lung biopsies to undergo WGA for mutational analysis. KRAS and CMET mutations have a deleterious effect on overall survival, hazard ratios 5.05 (p = 0.009) and 23.65 (p = 0.005), respectively. EGFR and p53 mutations, however, do not have a survival impact. There also does not seem to be significant differences in the frequency of mutations in EGFR, KRAS, and p53 between early- and advanced-stage disease: 20% versus 24% (p = 0.48), 29% versus 27% (p = 0.75), 10% versus 6% (p = 0.27), respectively. CONCLUSIONS: In advanced-stage NSCLC, KRAS, and CMET mutations suggest poor prognosis, whereas EGFR and p53 mutations do not seem to have survival impact. Mutations in EGFR, KRAS and p53 are unlikely to be responsible for the progression of NSCLC from early- to late-stage disease. WGA may be used to expand starting deoxyribonucleic acid from low-volume lung biopsies for further analysis of advanced-stage NSCLC.
机译：背景：非小细胞肺癌（NSCLC）从早期到晚期的进展可能预示着基因突变的积累。晚期肿瘤的突变谱也可能具有预后价值，指导治疗决策。从低容量诊断性肺活检中提取的脱氧核糖核酸含量低，限制了多个基因的突变检测。我们探索了全基因组扩增（WGA）以启用多种分子分析。方法：88例晚期NSCLC患者入组。他们的低容量肺活检标本经过WGA，然后直接测序表皮生长因子受体（EGFR），KRAS（大鼠肉瘤病毒），p53和CMET（间质-上皮转化因子）突变。检查了总体生存影响。对来自133名早期NSCLC患者的手术切除肿瘤的EGFR，KRAS和p53突变进行了测序。我们比较了两组的突变频率。结果：小批量肺活检进行WGA突变分析是可行的。 KRAS和CMET突变对总体生存具有有害影响，危险比分别为5.05（p = 0.009）和23.65（p = 0.005）。但是，EGFR和p53突变对生存没有影响。在早期和晚期疾病之间，EGFR，KRAS和p53的突变频率似乎也没有显着差异：20％对24％（p = 0.48），29％对27％（p = 0.75） ），分别为10％和6％（p = 0.27）。结论：在晚期NSCLC，KRAS和CMET突变提示预后较差，而EGFR和p53突变似乎对生存没有影响。 EGFR，KRAS和p53的突变不太可能是NSCLC从早期到晚期疾病发展的原因。 WGA可用于从小批量肺活检中扩增起始脱氧核糖核酸，以进一步分析晚期NSCLC。

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