在肺癌中使用滴滴数字聚合酶链反应进行KRAS突变的非侵入性分析
Reena Kishore1, Sonam N Kille1, Rhea Kishore2
1Department of Molecular Genetics and Cancer, Nitte University Centre for Science Education and Research, Nitte (Deemed to Be University), Deralakatte, Mangaluru, Karnataka.
概括
滴滴数字PCR (ddPCR) 在肺癌液体活检中有效检测KRAS突变. 这种敏感的方法有助于识别突变,这对于选择氨酸激酶抑制剂治疗至关重要.
科学领域:
- 癌症学
- 分子诊断
- 遗传学
背景情况:
- 全球肺癌发病率正在上升, 增加了对非侵入性诊断工具的需求.
- 液体活检为传统组织活检提供了不那么侵袭性的替代方案.
- 在肺癌中,KRAS突变是氨酸激酶抑制剂 (TKI) 治疗反应的关键预后标志物.
研究的目的:
- 在肺癌患者中使用滴滴数字PCR (ddPCR) 分析KRAS G12D,G12V和G13D突变.
- 从血液和瘤DNA中检测出KRAS突变之间的一致性.
- 评估ddPCR作为瘤学液体活检的临床工具的实用性.
主要方法:
- 使用基于探针的化学方法对KRAS G12D,G12V和G13D突变进行ddPCR试验的标准化.
- 从患者血液样本中提取无细胞DNA (cfDNA).
- 对血源cfDNA和瘤基因组DNA的ddPCR结果进行比较.
主要成果:
- 在分析的队列中观察到KRAS突变阳性率为81. 67%.
- 即使在低分数丰度的情况下,ddPCR也成功检测到cfDNA中的KRAS突变.
- 在血液cfDNA和瘤DNA分析中发现了66. 67%的一致率,这可能是由于瘤异质性.
结论:
- 在液体活检中检测罕见的瘤突变是一种高度敏感和有价值的工具.
- 这种技术可以作为肺癌突变分析的可行替代组织活检.
- 通过液体活检准确的KRAS突变概况可以显著帮助指导TKI治疗选择和改善患者的结果.
相关概念视频
02:38The Ras Gene
The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a superfamily...
Ras is a superfamily...
01:24Small GTPases - Ras and Rho
Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
Three regulatory proteins control their activity: