Dataset Information

HistoMosaic Detecting KRAS G12V Mutation Across Colorectal Cancer Tissue Slices through in Situ PCR.

ABSTRACT: 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.

SUBMITTER: Raub CB

PROVIDER: S-EPMC7446286 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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HistoMosaic Detecting KRAS G12V Mutation Across Colorectal Cancer Tissue Slices through in Situ PCR.

Raub Christopher B CB Lee Chen-Chung CC Shibata Darryl D Taylor Clive C Kartalov Emil E

Analytical chemistry 20160212 5

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 s ...[more]

PMID: 26820161

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Project description:IntroductionBefore anti-EGFR therapy is given to patients with colorectal cancer, it is required to determine KRAS mutation status in tumor. When tumor tissue is not available, cell-free DNA (liquid biopsy) is commonly used as an alternative. Due to the low abundance of tumor-derived DNA in cell-free DNA samples, methods with high sensitivity were preferred, including digital polymerase chain reaction, amplification refractory mutation system and next-generation sequencing. The aim of this systemic review and meta-analysis was to investigate the accuracy of those methods in detecting KRAS mutation in cell-free DNA sample from patients with colorectal cancer.MethodsLiterature search was performed in Pubmed, Embase, and Cochrane Library. After removing duplicates from the 170 publications found by literature search, eligible studies were identified using pre-defined criteria. Quality of the publications and relevant data were assessed and extracted thereafter. Meta-DiSc and STATA softwares were used to pool the accuracy parameters from the extracted data.ResultsA total of 33 eligible studies were identified for this systemic review and meta-analysis. After pooling, the overall sensitivity, specificity, and diagnostic odds ratio were 0.77 (95%CI: 0.74-0.79), 0.87 (95%CI: 0.85-0.89), and 23.96 (95%CI: 13.72-41.84), respectively. The overall positive and negative likelihood ratios were 5.55 (95%CI: 3.76-8.19) and 0.29 (95%CI: 0.21-0.38), respectively. Area under curve of the summarized ROC curve was 0.8992.ConclusionDigital polymerase chain reaction, amplification refractory mutation system, and next-generation sequencing had overall high accuracy in detecting KRAS mutation in cell-free DNA sample. Large prospective randomized clinical trials are needed to further convince the accuracy and usefulness of KRAS mutation detection using cfDNA/liquid biopsy samples in clinical practice.Trial registrationPROSPERO CRD42020176682; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=176682.

Dataset Information

HistoMosaic Detecting KRAS G12V Mutation Across Colorectal Cancer Tissue Slices through in Situ PCR.

Publications

HistoMosaic Detecting KRAS G12V Mutation Across Colorectal Cancer Tissue Slices through in Situ PCR.

Similar Datasets

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