Genome analysis of peeling archival cytology samples detects driver mutations in lung cancer
Genome analysis of peeling archival cytology samples detects driver mutations in lung cancer
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DOI：
10.1002/cam4.3089
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发表时间：
2020-07-01
期刊：
影响因子：
4
通讯作者：
Omata, Masao
中科院分区：
文献类型：
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作者：
Kunimasa, Kei;Hirotsu, Yosuke;Omata, Masao
当肿瘤组织样本无法搜索可操作的驱动突变时，存档细胞学样本可能是有用的。我们研究了与相应的福尔马林固定石蜡包埋（FFPE）肿瘤样本相比，档案细胞学样本是否能产生可靠的基因组信息。患者与方法从172例肺癌患者中选取具有足够肿瘤细胞的前处理V类细胞学档案样本。通过53个基因的全外显子组区域分析了原发性肺肿瘤的基因组图谱。我们比较了档案细胞学和相应原发肿瘤之间的致癌性和变异等位基因频率（VAF）的基因组图谱。我们还分析了EGFR-TKI治疗期间一系列细胞学样本的基因组图谱。结果对43例患者的配对样本进行了DNA突变分析，对3例患者的融合基因进行了分析。共检测到672个突变。其中，106个突变（15.8%）与两个样本共有。77例共有突变中有60例（77.9%）为致癌或可能致癌突变，VAF >= 10%。从档案细胞学样本中成功检测到高达90%（9/10）的可操作驱动突变和alkandros1融合基因。序列分析显示egfr - tki耐药突变（EGFRp.T790M）在治疗过程中发生了动态变化。结论与原发肿瘤相比，档案细胞学样本中有足够的肿瘤细胞可提供遗传信息。如果肿瘤组织样本不可用，我们可以使用存档细胞学样本来搜索可操作的驱动突变。
Introductions When tumor tissue samples are unavailable to search for actionable driver mutations, archival cytology samples can be useful. We investigate whether archival cytology samples can yield reliable genomic information compared to corresponding formalin-fixed paraffin-embedded (FFPE) tumor samples. Patients and Methods Pretreatment class V archival cytology samples with adequate tumor cells were selected from 172 lung cancer patients. The genomic profiles of the primary lung tumors have been analyzed through whole-exome regions of 53 genes. We compared the genomic profiles based on the oncogenicity and variant allele frequency (VAF) between the archival cytology and the corresponding primary tumors. We also analyzed the genomic profiles of serial cytological samples during the treatment of EGFR-TKI. Results A total of 43 patients were analyzed with the paired samples for DNA mutations and other three patients were analyzed for their fusion genes. A total of 672 mutations were detected. Of those, 106 mutations (15.8%) were shared with both samples. Sixty of seventy-seven (77.9%) shared mutations were oncogenic or likely oncogenic mutations with VAF >= 10%. As high as 90% (9/10) actionable driver mutations andALKandROS1fusion genes were successfully detected from archival cytology samples. Sequential analysis revealed the dynamic changes in EGFR-TKI-resistant mutation (EGFRp.T790M) during the course of treatment. Conclusion Archival cytology sample with adequate tumor cells can yield genetic information compared to the primary tumors. If tumor tissue samples are unavailable, we can use archival cytology samples to search for actionable driver mutations.