Genetic Instability Monitoring for Early Solid Tumor Risk Detection
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Solution Overview
Problem
Current methods lack the ability to effectively identify and monitor genetic conditions prodromal to the onset of solid tumors in healthy individuals, particularly due to insufficient understanding of genetic pathways and the limitations of existing techniques in analyzing circulating tumor DNA (ctDNA) for early detection.
Innovation Solution
A method utilizing next-generation sequencing (NGS) to analyze a panel of genes associated with solid tumors, including hotspots, in liquid biopsies such as blood or urine, to track mutation frequencies over time, providing a Key Risk Indicator through an algorithm that calculates genetic instability indices, and transitioning to early detection systems when necessary.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If next-generation sequencing is used to analyze circulating tumor DNA for early detection, then measurement precision of genetic mutations is improved, but device complexity and cost increase
Solution Approach 1:
The patent segments the complex sequencing task by focusing on specific gene panels (e.g., 50 genes associated with solid tumors) rather than whole-genome sequencing. This targeted approach maintains high detection sensitivity for cancer-relevant mutations while reducing the overall complexity and cost of the sequencing system.
Solution Approach 2:
The patent applies partial action by analyzing only the circulating tumor DNA fraction rather than total DNA, and by monitoring specific hotspots and driver genes rather than all possible mutations. This selective approach achieves sufficient detection precision for early cancer detection without requiring the full complexity of comprehensive genomic analysis.
2Reliability
If monitoring frequency is increased to improve early detection capability, then reliability of risk assessment is improved, but loss of time and resource consumption increase
Solution Approach 1:
The patent implements periodic monitoring at predetermined intervals (e.g., every 6-12 months) rather than continuous monitoring. This periodic approach maintains reliable risk assessment by capturing mutation accumulation over time while minimizing unnecessary resource consumption and patient burden during stable periods.
Solution Approach 2:
The patent uses feedback mechanisms where monitoring frequency and analytical sensitivity are dynamically adjusted based on detected mutation frequencies and risk levels. When mutation frequencies increase or risk indicators are detected, the system intensifies monitoring; when stable, it reduces frequency, optimizing both reliability and resource efficiency.
3Measurement precision
If analytical sensitivity is increased to detect lower frequency mutations, then measurement precision is improved, but loss of substance and false positives increase
Solution Approach 1:
The patent applies local quality by concentrating analytical sensitivity on specific regions of interest - namely, known cancer driver genes and hotspot mutations - rather than uniformly high sensitivity across all DNA. This targeted approach achieves high measurement precision for clinically relevant mutations while tolerating lower sensitivity elsewhere, reducing false positives.
Solution Approach 2:
The patent dynamically adjusts analytical sensitivity parameters based on the detected mutation frequency and clinical context. For low-frequency mutations in high-risk individuals, higher sensitivity is applied; for common variants or low-risk contexts, sensitivity is moderated to reduce false positives. This adaptive parameter adjustment optimizes the signal-to-noise ratio.
Data Source
Figure 2
AI summary
The method for searching and identifying a genetic condition prodromal of the onset of solid tumors in a healthy subject includes an evaluation cycle of a genetic stability or instability condition and at least one repetition cycle of said evaluation. The repetition cycles are carried out periodically on the subject, with the frequency depending on the result of the previous cycle. Each cycle includes the steps of: - taking a sample of biological material, isolating the DNA from the biological material, amplifying and sequencing the isolated DNA; - verifying the presence of mutations selected in a predetermined set of genes of the sample under consideration, said set of genes and said mutations being associated with the onset of solid tumors; - the predetermined set of genes including either a subset of the panel of genes or hotspots connected to one or more solid tumors, or the entire panel of genes connected to solid tumors; - verifying the frequency of mutations detected for each gene and for each evaluation cycle, the mutations being selected from the aforementioned selected mutations; - recording the mutations detected for each gene or group of genes and their frequency; - defining or updating a genetic instability index of the subject, either overall (IT) or for a single gene (IG), for each repetition cycle, based on the frequency of mutations detected and on the basis of the increase in the frequency of mutations; - evaluating, in each repetition cycle, the subject's entry into a prodromal genetic condition upon the onset of one or more solid tumors or groups of solid tumors on the basis of a threshold value (ITS,JGS) of the genetic instability index (IT,JG), defined for each single gene or group of genes, being exceeded.