Non-invasive Colon Cancer Detection via Fecal DNA Mutational Analysis

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Solution Overview

Problem

Current methods for detecting colon cancer and precursor cells are invasive, unreliable, or too costly, particularly when using fecal samples, as they face challenges with primer interactions and the presence of wild-type and mutated DNA, limiting non-invasive early detection capabilities.

Innovation Solution

A method involving the use of specific primers for APC, K-ras, β-catenin, and B-raf genes through PCR amplification and mutational analysis in fecal or tissue samples, allowing for non-invasive, reliable, and cost-effective detection of colon cancer and precursor cells by analyzing DNA from these samples.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If multiple primers are combined to detect multiple mutations in feces, then detection coverage is improved, but primer interactions with fecal components and among themselves cause masking effects that reduce reliability

Engineering Contradiction:
Improvedetection coverageVSAvoiddetection reliability
Core Design Contradiction:
Adaptability or versatilityVSReliability

Solution Approach 1:

The patent divides the detection system into separate primer sets, each optimized for specific mutation types or gene regions. This segmentation allows each primer to be tailored for its specific target, reducing unwanted interactions and masking effects while maintaining comprehensive detection coverage across multiple genes and mutation types.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent applies local quality by designing primers with specific characteristics optimized for their particular targets. Each primer set is locally optimized for its specific gene or mutation type, with considerations for fecal sample interference, primer binding specificity, and detection sensitivity tailored to each region's requirements.

Inventive Principle:
Principle #3Local quality

2Measurement precision

If direct sequencing of PCR products is performed on fecal samples, then mutational analysis is achieved, but the presence of wild-type and mutated DNA makes reliable detection difficult

Engineering Contradiction:
Improvemutational analysis precisionVSAvoiddetection reliability
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The patent extracts and isolates specific DNA regions containing mutations through targeted PCR amplification using gene-specific primers. This extraction concentrates the mutated DNA sequences away from the background of wild-type DNA and other fecal components, enabling reliable detection through subsequent sequencing or hybridization analysis.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent performs preliminary PCR amplification to enrich for mutated DNA sequences before final sequencing or detection. This preliminary action concentrates the signal by amplifying only the regions of interest, making subsequent analysis more reliable despite the presence of wild-type DNA in the original fecal sample.

Inventive Principle:
Principle #10Preliminary action

3Reliability

If invasive methods such as colonoscopy are used for detection, then detection reliability is improved, but patient comfort and ease of testing are worsened

Engineering Contradiction:
Improvedetection reliabilityVSAvoidtesting convenience
Core Design Contradiction:
ReliabilityVSEase of operation

Solution Approach 1:

The patent uses fecal DNA as an intermediary medium to detect colon cancer mutations without requiring direct visualization or biopsy of the colon tissue. The fecal sample serves as a non-invasive proxy that contains circulating tumor DNA, enabling reliable detection while maintaining patient comfort and ease of testing.

Inventive Principle:
Principle #24Intermediary (Mediator)

4Measurement precision

If comprehensive mutation testing is performed, then detection sensitivity is improved, but test cost increases significantly

Engineering Contradiction:
Improvedetection sensitivityVSAvoidtest cost
Core Design Contradiction:
Measurement precisionVSEase of manufacture

Solution Approach 1:

The patent employs a universal detection platform that can identify multiple mutation types and gene regions using a single integrated assay system. This multi-functionality allows comprehensive mutation testing without proportionally increasing cost, as the same basic methodology and reagents can be applied across different genes and mutation types through standardized protocols.

Inventive Principle:
Principle #6Universality (Multi-functionality)

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 method enables early and reliable detection of colon cancer with high sensitivity and specificity, comparable to colonoscopy, while being non-invasive and cost-effective, allowing for routine testing and prophylactic examinations.

Implementation Method 1

performing an amplification reaction, preferably a PCR reaction, in the genes for APC, K-ras, β-catenin and B-raf

Methodology Applied
Scientific EffectPolymerase chain reaction (PCR):

Implementation Method 2

performing a mutational analysis in the amplification products

Methodology Applied
Scientific EffectMutational analysis:

Data Source

PatentUS7833757B2Method for conducting non-invasive early detection of colon cancer and/or of colon cancer precursor cells
Publication Date: 2010.11.16 UNIV POSTDAM

AI summary

The invention relates to a method for conducting non-invasive early detection of colon cancer and/or of colon cancer precursor cells, by using primers with which mutation analyses can be carried out in selected regions of genes APC, K-ras, β-catenin and B-raf. The invention also relates to a kit containing said primers, and to the use of these primers and of the kit for analyzing mutations, particularly for conducting the early detection of colon cancer and/or of colon cancer precursory cells.