Lim Elaine H, Zhang Shen-Li, Li Jia-Liang, Yap Wee-See, Howe Tse-Chiang, Tan Bien-Peng, Lee Yong-Shyan, Wong Daniel, Khoo Kay-Leong, Seto Kar-Yin, Tan Lenny, Agasthian Thirugananam, Koong Heng-Nung, Tam John, Tan Christie, Caleb Michael, Chang Alex, Ng Alan, Tan Patrick
Johns Hopkins Singapore International Medical Centre, Singapore.
J Thorac Oncol. 2009 Jan;4(1):12-21. doi: 10.1097/JTO.0b013e3181913e28.
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.
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.
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.
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.
非小细胞肺癌（NSCLC）从早期发展到晚期可能意味着基因突变的积累。晚期肿瘤的突变谱也可能具有预后价值，可指导治疗决策。从低容量诊断性肺活检中提取的脱氧核糖核酸量较少，限制了多个基因的突变检测。我们探索了全基因组扩增（WGA）以进行多种分子分析。
纳入88例晚期NSCLC患者。对其低容量肺活检标本进行WGA，然后直接测序检测表皮生长因子受体（EGFR）、KRAS（大鼠肉瘤病毒）、p53和CMET（间充质上皮转化因子）的突变情况。检查对总生存期的影响。对133例早期NSCLC患者手术切除的肿瘤进行EGFR、KRAS和p53突变测序。我们比较了两组的突变频率。
低容量肺活检标本进行WGA用于突变分析是可行的。KRAS和CMET突变对总生存期有有害影响，风险比分别为5.05（p = 0.009）和23.65（p = 0.005）。然而，EGFR和p53突变对生存期没有影响。早期和晚期疾病中EGFR、KRAS和p53的突变频率似乎也没有显著差异：分别为20%对24%（p = 0.48）、29%对27%（p = 0.75）、10%对6%（p = 0.27）。
在晚期NSCLC中，KRAS和CMET突变提示预后不良，而EGFR和p53突变似乎对生存期没有影响。EGFR、KRAS和p53的突变不太可能是NSCLC从早期发展到晚期疾病的原因。WGA可用于扩增低容量肺活检标本中的起始脱氧核糖核酸，以进一步分析晚期NSCLC。
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