Methylated DNA Detection for Colorectal Cancer Screening
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Solution Overview
Problem
Current methods for detecting colorectal cancer (CRC) are invasive, have low sensitivity and specificity, and often miss early-stage cancers due to limited availability of circulating tumor DNA.
Innovation Solution
The method involves detecting DNA methylation at specific CpG dinucleotides within the mANKRD13B and/or mSEPTIN9 target regions in biological samples using bisulfite conversion and methylation-specific PCR, allowing for the early and reliable detection of CRC.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If conventional stool-based tests (FIT or gFOBT) are used for CRC detection, then the test can be performed non-invasively, but the sensitivity and specificity are relatively low
Solution Approach 1:
The patent replaces mechanical/stool-based detection methods with molecular biology-based detection. Instead of detecting blood or polyps in stool samples, the invention detects methylated DNA sequences (ANKRD13B and SEPTIN9) in blood or body fluid samples using PCR techniques. This substitution enables early-stage cancer detection with higher sensitivity and specificity while maintaining non-invasive sampling through blood draws.
2Measurement precision
If visual exams (colonoscopy or sigmoidoscopy) are performed for CRC detection, then the sensitivity is high, but the procedure is invasive and uncomfortable
Solution Approach 1:
The patent uses blood or body fluid samples as an intermediary medium to detect CRC markers. Instead of directly examining the colon interior through invasive scopes, the invention detects methylated DNA sequences in blood samples that originate from tumor cells. This intermediary approach maintains high detection sensitivity while eliminating the invasiveness and discomfort associated with visual exams.
3Ease of operation
If non-invasive imaging techniques are used for CRC detection, then the procedure is comfortable, but the sensitivity is low and small polyps are often missed
Solution Approach 1:
The patent replaces imaging techniques with molecular detection methods. Instead of using radiation-based imaging that has low sensitivity for small polyps, the invention uses PCR-based detection of methylated DNA sequences (ANKRD13B and SEPTIN9) in blood samples. This substitution achieves high sensitivity for early-stage cancer detection while maintaining the comfort of non-invasive sampling.
4Reliability
If early-stage cancer is detected, then the 5-year relative survival rate is about 90%, but the amount of circulating tumor DNA is limited and harder to detect
Solution Approach 1:
The patent changes the detection parameter from total DNA amount to methylation status. Instead of relying on the quantity of circulating tumor DNA (which is limited in early stages), the invention detects the methylation state of specific genes (ANKRD13B and SEPTIN9). This parameter change enables sensitive detection of early-stage cancer because methylation patterns are distinctive and can be detected even when tumor DNA quantity is low.
Solution Approach 2:
The patent focuses detection on specific local regions (CpG sites) within the genome rather than analyzing total DNA. By targeting specific methylated regions of ANKRD13B and SEPTIN9 genes, the invention achieves high detection sensitivity in early-stage cancer where overall circulating tumor DNA is limited. This localized quality approach concentrates detection power on the most informative genomic regions.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
This approach significantly improves the sensitivity and specificity of CRC detection, enabling early diagnosis and monitoring of the disease with high accuracy.
Implementation Method 1
The method involves detecting DNA methylation at specific CpG dinucleotides within the mANKRD13B and/or mSEPTIN9 target regions in biological samples using bisulfite conversion and methylation-specific PCR
Implementation Method 2
The method involves detecting DNA methylation at specific CpG dinucleotides within the mANKRD13B and/or mSEPTIN9 target regions in biological samples using bisulfite conversion and methylation-specific PCR
Data Source
AI summary
The present invention relates to the field of pharmacogenomics and in particular to detecting the presence or absence of methylated ANKRD13B and/or SEPTIN9 DNA derived from a tumor in blood or blood-derived samples or in other body fluids that contain DNA released from a tumor. This detection is useful for a minimally or non-invasive as well as early and reliable diagnosis of colorectal cancer. The invention provides methods and oligonucleotides suitable for this purpose.