试点研究:低通全基因组测序的无尿细胞DNA可以检测和分子类型上道泌尿道皮质癌
Chaz Quinn1, L Angelica Lerma1, Alexander Zhu2
1Department of Laboratory Medicine & Pathology, University of Washington, Seattle, WA, US.
American journal of clinical pathology
|February 9, 2025
概括
尿液无细胞瘤DNA (cfDNA) 与瘤组织具有很高的一致性,用于检测上道泌尿瘤 (UTUC) 的遗传异常. 这种非侵入性生物标志物为UTUC诊断和监测提供了一个有前途的工具.
科学领域:
- 基因组学就是基因组学.
- 在瘤学瘤学.
- 分子诊断学 分子诊断
背景情况:
- 上管泌尿道癌 (UTUC) 由于难以进行活检和往往晚期诊断,因此存在诊断挑战.
- 目前用于UTUC的诊断方法可以产生非诊断结果,导致患者的治疗结果不佳.
- 无细胞瘤DNA (cfDNA) 显示出改善早期诊断,异质性评估和UTUC监测的潜力,但其在尿液中的实用性尚未确定.
研究的目的:
- 为了检测UTUC的细胞遗传异常,使用cfDNA的低通全基因组测序 (LPWGS).
- 为了比较尿源和血cfDNA与瘤组织的有效性,以识别与UTUC相关的基因组变化.
- 评估尿液cfDNA作为UTUC的非侵入性生物标志物的可行性.
主要方法:
- 低通全基因组测序 (LPWGS) 在从4名UTUC患者的尿液和血中提取的cfDNA上进行.
- 基因组DNA也从匹配的瘤组织中提取出来进行比较.
- 在cfDNA样本和瘤组织之间进行了对应分析,以检测基因组异常.
主要成果:
- 异常基因组区域在瘤组织中最为丰富,其次是尿液cfDNA,然后是血cfDNA.
- 尿液cfDNA显示出与瘤组织的染色体和亚染色体变化高度一致 (r = 0.88-0.99),与血cfDNA不同 (r < 0.25).
- 尿液cfDNA的LPWGS显示了94%的重叠与已知的UTUC相关基因,突出了其诊断潜力.
结论:
- 在LPWGS分析时,尿液cfDNA在识别UTUC相关基因异常方面优于血cfDNA.
- 排尿cfDNA中的分子特征在染色体和亚染色体水平上与瘤组织密切匹配.
- 尿液cfDNA是一种可行的非侵入性生物标志物,用于检测和监测UTUC.
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