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Updated: Jan 31, 2026
08:30
Preparation of Formalin-fixed Paraffin-embedded Tissue Cores for both RNA and DNA Extraction
Published on: August 21, 2016
52.0K
Structural Variation Detection by Proximity Ligation from Formalin-Fixed, Paraffin-Embedded Tumor Tissue
Christopher J Troll1, Nicholas H Putnam1, Paul D Hartley1
1Division of Research and Development, Dovetail Genomics, LLC, Santa Cruz, California.
The Journal of Molecular Diagnostics : JMD
|January 4, 2019
Summary
A new Fix-C method detects genetic variations in fragmented DNA from FFPE cancer samples. This breakthrough enables structural variation detection and aids in developing targeted molecular diagnostics for improved patient care.
Area of Science:
- Oncology
- Genomics
- Molecular Biology
Background:
- Clinical management of solid tumors relies on detecting genetic variations.
- Formalin-fixed, paraffin-embedded (FFPE) samples contain fragmented and damaged DNA, hindering genetic analysis.
- Current technologies cannot generate long-range DNA sequence data from degraded DNA for structural variation detection.
Purpose of the Study:
- To develop a novel method for detecting genetic variations in FFPE samples.
- To enable structural variation detection and long-range genotype phasing from archival FFPE specimens.
- To overcome the limitations of analyzing fragmented DNA in FFPE samples for cancer diagnostics.
Main Methods:
- Development of a high-throughput chromosome conformation capture approach named Fix-C.
- Application of Fix-C to 15 clinical adenocarcinoma and sarcoma FFPE specimens.
- Comparison of Fix-C results with fluorescence in situ hybridization (FISH) assays.
Main Results:
- Fix-C achieved a 90% concordance rate with FISH assays, the clinical gold standard.
- Novel structural variations, previously undetected by other methods, were identified.
- Long-range chromatin configuration information was recovered from FFPE samples with highly degraded DNA.
Conclusions:
- Fix-C is a powerful approach for detecting structural variations in FFPE samples.
- This method enables detailed resolution of global genome rearrangement events in cancer progression.
- Fix-C will inform the development of targeted molecular diagnostic assays for patient care.
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