Genomic Instability Score for HR Deficiency Detection
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
There is an unmet need for methods to detect homologous recombination deficiency and predict treatment response in basal-like, luminal, and HER2-overexpressing breast carcinomas, as well as other cancers, as current methods are inadequate for early diagnosis and prognosis.
Innovation Solution
A method involving the detection of large-scale chromosome breaks to quantify DNA rearrangements in tumor samples, which correlates with HR pathway deficiency, allowing for the prediction of BRCA1 and BRCA2 gene status and response to specific cancer treatments such as PARP inhibitors and DNA damaging agents.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If current methods are used for detecting homologous recombination deficiency, then the diagnostic process is simple, but the measurement precision and reliability are insufficient for early diagnosis and prognosis
Solution Approach 1:
The patent introduces a genomic instability score as an intermediary metric that quantifies chromosomal rearrangements. This score serves as a mediator between the complex genomic analysis and the clinical diagnosis of HR deficiency, transforming complex genomic data into a reliable diagnostic indicator that predicts treatment response to PARP inhibitors and DNA-damaging agents
Solution Approach 2:
The patent changes the detection parameter from simple presence/absence of mutations to a quantitative genomic instability score based on chromosomal rearrangements. This parameter transformation enables more precise measurement of HR pathway dysfunction while providing a continuous variable for risk stratification and treatment prediction
2Reliability
If comprehensive genomic analysis is performed to detect rearrangements, then the reliability of HR deficiency detection is improved, but the loss of time and complexity of operation increase
Solution Approach 1:
The patent extracts the essential diagnostic information by focusing specifically on chromosomal rearrangements and genomic instability scoring, rather than analyzing all possible genomic alterations. This extraction of key features maintains high reliability for HR deficiency detection while reducing the time and computational resources required compared to comprehensive genomic sequencing
Solution Approach 2:
The patent performs preliminary genomic instability assessment to identify patients likely to benefit from PARP inhibitors or DNA-damaging agents before initiating treatment. This preliminary action enables early stratification of patients based on HR pathway status, allowing clinicians to select appropriate therapies upfront and avoid trial-and-error treatment approaches
Data Source
Figure 1
Figure 2
Figure 3a~3b
AI summary
The invention relates to methods for detecting inactivation of the DNA Homologous Recombination pathway in a patient, and in particular for detecting BRCA1 inactivation.