Raub Christopher B, Lee Chen-Chung, Shibata Darryl, Taylor Clive, Kartalov Emil
Department of Pathology, Keck School of Medicine of the University of Southern California , 2011 Zonal Avenue, Los Angeles, California 90089, United States.
Anal Chem. 2016 Mar 1;88(5):2792-8. doi: 10.1021/acs.analchem.5b04460. Epub 2016 Feb 12.
We report on HistoMosaic, a novel technique for genetic analysis of formalin-fixed, paraffin-embedded tissue slices. It combines microfluidic compartmentalization, in situ allele-specific PCR, and fluorescence microscopy. The experimental proof of principle was achieved by in situ detection of KRAS G12V mutation in colorectal cancer tissues and is presented herein. HistoMosaic offers the ability to detect mutations over the entire tissue slide simultaneously, rapidly, economically, and without selection bias, while coregistering the genetic information with the preserved morphological information. Thus, HistoMosaic has wide applicability in basic science as a tool to map genetic heterogeneity. It is also a platform to build companion diagnostics for targeted therapies in oncology, to help ensure that the right drug is given to the right patient, thereby saving healthcare resources and improving patient outcomes.
我们报告了HistoMosaic，这是一种用于福尔马林固定、石蜡包埋组织切片基因分析的新技术。它结合了微流控分隔、原位等位基因特异性PCR和荧光显微镜技术。通过对结直肠癌组织中KRAS G12V突变的原位检测实现了原理的实验验证，并在此展示。HistoMosaic能够在整个组织切片上同时、快速、经济且无选择偏倚地检测突变，同时将遗传信息与保留的形态学信息进行配准。因此，HistoMosaic作为一种绘制基因异质性的工具在基础科学中具有广泛的适用性。它也是一个构建肿瘤靶向治疗伴随诊断的平台，有助于确保将正确的药物给予正确的患者，从而节省医疗资源并改善患者预后。
