CTCF-Binding Site Mutation Analysis for Gastrointestinal Cancer Risk
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Solution Overview
Problem
Current cancer genomics studies primarily focus on somatic DNA alterations in protein-coding regions, largely ignoring non-coding regions, which are crucial for regulating gene expression and maintaining chromosomal architecture, leading to a lack of understanding of non-coding tissue-specific driver mutations in gastrointestinal cancers.
Innovation Solution
A method is developed to determine the risk of gastrointestinal cancer by analyzing mutations in specific CTCF-binding sites and non-CBS regions, using primers with at least 85% sequence identity to detect mutations in biological samples, indicating the presence of mutations indicative of cancer risk.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If cancer genomics studies focus on profiling somatic DNA alterations in protein coding regions, then the cost is reduced and the analysis is simplified, but the non-coding regions which harbor crucial functional elements are ignored and the understanding of cancer development is incomplete
Solution Approach 1:
The patent segments the non-coding genome into specific functional regions of interest, including CTCF-binding sites, enhancers, promoters, and other regulatory elements. This segmentation allows targeted analysis of these critical regions without requiring costly whole-genome sequencing, thus resolving the contradiction between ease of analysis and information completeness.
Solution Approach 2:
The patent applies local quality by focusing analytical resources on specific non-coding regions known to have high functional significance, such as CTCF-binding sites and tissue-specific enhancers. This targeted approach concentrates sequencing depth and analytical effort where it matters most for cancer driver identification, balancing cost efficiency with comprehensive information capture.
2Reliability
If hundreds of samples are analyzed to identify tissue-specific non-coding driver mutations, then the statistical power is sufficient, but the time and resources required are excessive
Solution Approach 1:
The patent performs preliminary action by pre-identifying and cataloging tissue-specific non-coding regions with high prior probability of containing driver mutations, such as conserved enhancers and CTCF-binding sites. This preliminary characterization of the non-coding landscape allows subsequent studies to focus only on these pre-selected regions, reducing the sample size needed for statistically reliable detection while maintaining high confidence in identified drivers.
Solution Approach 2:
The patent changes the parameter of analysis from whole-genome or exome sequencing to targeted sequencing of specific non-coding regions. This parameter change increases the effective sequencing depth and statistical power per dollar spent, enabling reliable identification of tissue-specific drivers with fewer samples and less time while maintaining or improving detection sensitivity.
3Loss of information
If comprehensive genetic and molecular profiling is performed on gastrointestinal cancer, then the understanding of disease development is enhanced, but the cost and complexity of the study increase
Solution Approach 1:
The patent extracts and isolates the specific non-coding elements most relevant to gastrointestinal cancer development, including tissue-specific enhancers, CTCF-binding sites, and other regulatory regions. By extracting only these critical elements for analysis rather than performing comprehensive whole-genome sequencing, the study achieves enhanced understanding of disease development while reducing both cost and analytical complexity.
Data Source
AI summary
There is provided a method of determining a risk of gastrointestinal cancer in a human subject, the method comprising: determining in a biological sample of the subject, whether mutation is present in at least one CTCF-binding sites (CBS) overlapping regions, or portions or flanking sequences thereof, or at least one non-CBS regions, or portions or flanking sequences thereof, wherein presence of mutation in at least one CBS overlapping regions, or portions or flanking sequences thereof, and/or at least one non-CBS regions, or portions or flanking sequences thereof, is indicative of a risk of gastrointestinal cancer in the subject. There are also provided a method of treating gastrointestinal cancer in a human subject and related kits.