Next-generation sequencing analysis of endometrial screening liquid-based cytology specimens: a comparative study to tissue specimens
Next-generation sequencing analysis of endometrial screening liquid-based cytology specimens: a comparative study to tissue specimens
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DOI：
10.1186/s12920-020-00753-6
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发表时间：
2020-07-11
影响因子：
2.7
通讯作者：
Tanimoto, Akihide
中科院分区：
文献类型：
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作者：
Akahane, Toshiaki;Kitazono, Ikumi;Tanimoto, Akihide
背景 液基细胞学（LBC）现在是一种广泛使用的细胞学筛查和癌症诊断方法。由于细胞是用酒精固定剂固定的，并且标本储存在液体条件下，因此 LBC 标本适合用于遗传分析。方法在这里，我们建立了一个小型癌症基因组，包括用于下一代测序的60个基因和17个微卫星标记，并将其应用于子宫内膜癌筛查获得的残留LBC标本，以与相应的福尔马林固定石蜡包埋（FFPE）组织进行比较。结果 共分析了 49 例 FFPE 和 LBC 标本（n = 24），揭示了子宫内膜癌的特征突变，包括 PTEN、CTNNB1、PIK3CA 和 PIK3R1 突变。八个病例的肿瘤突变负荷（TMB）和微卫星不稳定性（MSI）得分较高，这与缺陷错配修复（MMR）蛋白表达一致。 7 例配对的子宫内膜 LBC 以及活检和/或切除的 FFPE 组织在所有病例中均呈现几乎相同的突变、TMB 和 MSI 特征。结论 这些发现表明，我们的特设癌症基因组能够检测子宫内膜 LBC 和 FFPE 标本中可治疗的基因突变。子宫内膜癌 LBC 标本提供了一种替代且经济实惠的分子检测材料来源。
Background Liquid-based cytology (LBC) is now a widely used method for cytologic screening and cancer diagnosis. Since the cells are fixed with alcohol-based fixatives, and the specimens are stored in a liquid condition, LBC specimens are suitable for genetic analyses. Methods Here, we established a small cancer gene panel, including 60 genes and 17 microsatellite markers for next-generation sequencing, and applied to residual LBC specimens obtained by endometrial cancer screening to compare with corresponding formalin-fixed paraffin-embedded (FFPE) tissues. Results A total of 49 FFPE and LBC specimens (n = 24) were analyzed, revealing characteristic mutations for endometrial cancer, includingPTEN, CTNNB1, PIK3CA,andPIK3R1mutations. Eight cases had higher scores for both tumor mutation burden (TMB) and microsatellite instability (MSI), which agree with defective mismatch repair (MMR) protein expression. Paired endometrial LBC, and biopsied and/or resected FFPE tissues from 7 cases, presented almost identical mutations, TMB, and MSI profiles in all cases. Conclusion These findings demonstrate that our ad hoc cancer gene panel enabled the detection of therapeutically actionable gene mutations in endometrial LBC and FFPE specimens. Endometrial cancer LBC specimens offer an alternative and affordable source of molecular testing materials.