靶向测序技术对铂类耐药卵巢癌多基因检测分析

Analysis of Targeted Sequencing Technology on Multiple Gene Detection of Platinum Resistant Ovarian Cancer

目的:了解铂类耐药晚期卵巢上皮癌患者癌症相关的50个基因突变状态。方法:使用高通量测序技术,选择美国国立综合癌症网络(NCCN)提出的与肿瘤用药、致癌基因通路及肿瘤检测相关的50个基因、256个热点突变位点进行检测,分析铂类耐药卵巢上皮癌患者50个基因的突变状态,包括基因突变类型、突变率、错义突变数和错义突变发生率。结果:15例标本的50个基因的检测中,17个基因发生突变,突变率32%,每个标本平均有7.47个突变,其中PDGFRA、RET是最常见基因突变类型;在17个基因112个突变中,共检出错义突变16个,缺失突变4个,错义突变中TP53发生率为68.75%(12/16),PIK3CA、KRAS、SMAD4、EGFR各检出1个错义突变,缺失突变中均为TP53基因突变;7例标本中检出EGFR9个突变,8例同义突变,1例错义突变,其中EGFR基因错义突变为外显子21 L858R。结论:铂类耐药卵巢上皮癌中TP53基因突变可能是最常见的错义和缺失突变,EGFR外显子21L858R突变使用埃克替尼有效,提示对于晚期卵巢癌EGFR敏感基因突变,可尝试行EGFR-TKIs治疗。

Objective： To understand 50 gene mutation status related to patients with platinum resist- ant critical stage ovarian epithelial cancer. Methods： Adopting high-throughput sequencing technology to detect 50 genes, 256 hot-spot mutant sites related to antitumor drugs, oncogene pathways, and tumor detection proposed by NCCN ; analyzing 50 gene mutation status related to patients with platinum resistant critical stage ovarian epithelial cancer, including mutant types, mutation rate, missense muta- tions number and its incidence rate. Results： Of all 50 genes detection of 15 samples, 17 genes were mutated, the mutation rate was 32% ; average 7.47 mutations in each sample, which PDGFRA and RET are the most common mutations. Of all the 112 mutations in 17 genes, 16 missense mutations and 4 deletion mutations were detected. The missense mutation TP53 incidence rate is 68.75% （12/16）, and one missense mutation is detected in PIK3CA, KRAS, SMAD4 and EGFR. Deletion mutations were all TP53 gene mutation. 9 EGFR mutations were detected in 7 samples, among which 8 samples were synonymous mutations and 1 sample was rnissense mutation. The EGFR missense mutations locus was exon 21 L858R. Conclusion： TP53 mutation might be the most common missense and deletion mutations in platinum resistant ovarian epithelial cancer. The effective use of Icotinih in EGFR exon21L858R showed the use of EGFR-TKIs treatment could be possible for the sensitive gene mutation in critical stage ovarian cancer.