TP53 Probe Library for Early dPCR Relapse Detection
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Solution Overview
Problem
Existing digital PCR (dPCR) probes lack flexibility and are limited to detecting only highly frequent specific sequences, making it difficult to quickly diagnose cancer relapses due to individual-specific mutations in the TP53 gene, particularly in esophageal, gastric, and colorectal cancers.
Innovation Solution
A library of 29 sets of probes and primers designed to detect various mutations in the TP53 gene, including non-intermittent complementarity, enabling early detection of cancer relapses through digital PCR analysis.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If commercially available dPCR probes are designed to be complementary to continuous nucleotide sequences at intervals, then manufacturing simplicity is improved, but adaptability to various individual-specific mutations deteriorates
Solution Approach 1:
The invention segments the TP53 gene into multiple regions and designs specific probes for each segment. This allows comprehensive coverage of various mutations while maintaining systematic organization. The segmented approach enables the probe set to detect different mutation types (c.524G>A, c.743G>A, c.818G>A, etc.) that would be missed by continuous sequence probes.
Solution Approach 2:
The probe set is designed to serve multiple functions: detecting wild-type sequences, detecting various mutant sequences, and providing comprehensive mutation screening across the TP53 gene. Each probe is specifically designed to bind to particular sequence variants, enabling a single probe set to handle diverse mutation scenarios in esophageal, gastric, and colorectal cancers.
2Device complexity
If existing dPCR probes are used for detection, then device complexity is reduced, but measurement precision for individual-specific mutations deteriorates
Solution Approach 1:
Each probe is designed with local quality optimized for its specific target sequence. The probes contain specific nucleotide sequences that complementarily bind to particular mutation sites (e.g., c.524G>A, c.743G>A). This local optimization ensures high binding affinity and specificity for each mutation type, achieving precise detection without requiring complex instrumentation.
3Adaptability or versatility
If comprehensive probe libraries are prepared to respond to various mutations, then adaptability improves, but device complexity and cost increase
Solution Approach 1:
The invention adds a dimensional organization to the probe library by categorizing probes according to specific mutation sites (c.524, c.743, c.818, c.817, c.742, c.844, c.637, c.733, c.747, c.659). This systematic dimensionality allows comprehensive mutation coverage while maintaining manageable library structure through clear categorization and indexing of probes by their target sequences.
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
The library allows for the early detection of cancer relapses in about 90% of patients, particularly in esophageal, gastric, and colorectal cancers, by identifying mutations in circulating tumor DNA.
Implementation Method 1
a probe (SEQ ID NO: 3) complementary to a specific sequence in a DNA fragment amplified with primers (usually one nucleotide) is used to detect the specific sequence
Implementation Method 2
a probe complementary to a specific sequence in a DNA fragment amplified with primers
Data Source
AI summary
An object is to provide a versatile means utilizing a probe for dPCR, which enables quick detection of a mutation relevant to a cancer. A library including a plurality of probes and/or primers or primer pairs for detecting a mutation relevant to a cancer in the DNA-binding domain of the TP53 gene is provided. By using the present invention, relapse of alimentary canal cancer after treatment can be diagnosed at an early stage. Individualized post-treatment follow-up of an alimentary canal cancer patient is also enabled.