BRAF and TERT Mutation Detection for Aggressive Thyroid Cancer
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Solution Overview
Problem
Current methods for managing aggressive papillary thyroid cancer (PTC) lack effective molecular-based strategies due to unclear genetic mechanisms underlying its aggressiveness, particularly the coexistence of BRAF and TERT mutations.
Innovation Solution
A method involving genetic testing to identify the coexistence of BRAF V600E and TERT promoter mutations in patients, using sequencing techniques to amplify and detect specific mutations in DNA samples, allowing for targeted treatment modalities such as thyroidectomy, radioactive iodine therapy, or inhibitors of TERT and BRAF pathways.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional management methods are used for aggressive PTC, then treatment can be provided, but prognosis remains poor due to lack of molecular-based strategies
Solution Approach 1:
The patent performs genetic testing for BRAF and TERT mutations before treatment decisions are made. This preliminary molecular characterization allows clinicians to identify aggressive PTC cases early and apply targeted therapies beforehand, improving prognosis by preventing disease progression rather than reacting to it later.
Solution Approach 2:
The patent applies different treatment approaches based on the specific genetic profile of each patient's tumor. By identifying local molecular characteristics (BRAF mutation status, TERT promoter mutations), the management strategy is customized to the specific genetic subtype, providing more effective targeted therapy rather than uniform conventional treatment.
2Measurement precision
If genetic testing for BRAF and TERT mutations is performed, then precise identification of aggressive PTC is achieved, but diagnostic complexity and cost increase
Solution Approach 1:
The patent divides the diagnostic process into distinct modular steps: DNA extraction from clinical samples, PCR amplification of specific gene regions (BRAF exon 15 and TERT promoter), and sequencing analysis. Each step can be performed independently with standardized protocols, making the complex diagnostic process more manageable and implementable in clinical settings.
Solution Approach 2:
The patent uses PCR amplification as an intermediary step between DNA extraction and sequencing. This intermediary process enriches the specific genomic regions of interest (BRAF and TERT) from the complex genomic background, enabling precise detection of mutations while simplifying the overall diagnostic workflow by focusing only on relevant sequences.
3Reliability
If targeted therapies based on mutation status are applied, then treatment effectiveness is improved, but treatment options and decision-making complexity increase
Solution Approach 1:
The patent implements a feedback loop where treatment decisions are continuously guided by molecular test results. The genetic profile (BRAF mutation status, TERT promoter mutations) provides feedback that informs which targeted therapy to select, and treatment response can be monitored through repeat molecular testing, allowing dynamic adjustment of therapy to maintain effectiveness.
Solution Approach 2:
The patent changes the fundamental parameter used for treatment selection from clinical/anatomical features to molecular genetic parameters. By using mutation status (presence/absence of BRAF V600E, TERT promoter mutations) as the decision parameter, the system simplifies treatment selection despite the availability of multiple therapeutic options, as the molecular profile directly guides therapy choice.
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 approach enables precise identification and treatment of aggressive PTC cases, improving prognosis and management by targeting the unique genetic background of aggressive tumors, thereby enhancing disease-free survival and reducing recurrence rates.
Implementation Method 1
amplifying by polymerase chain reaction (PCR) a region of the TERT gene that comprises −124 and −146 from the translation start site in the promoter of TERT and a region of the BRAF gene that comprises the T1779A nucleotide site
Implementation Method 2
sequencing the amplification product to identify the presence of the C228T, C250T and/or the V600E mutation
Data Source
AI summary
The present invention relates to the field of cancer. More specifically, the present invention provides methods and compositions related to certain mutations in cancer. In one embodiment, a method for treating a subject having aggressive thyroid cancer comprises the steps of (a) obtaining a biological sample from the subject; (b) performing an assay on the sample obtained from the subject to identify a mutation at 1 295 228 C>T (C228T), corresponding to −124 C>T from the translation start site in the promoter of the telomerase reverse transcriptase (TERT) gene, and a T1799A mutation in the BRAF gene that results in a V600E amino acid change; (c) identifying the subject as having or likely to develop aggressive thyroid cancer if the C228T and V600E mutations are identified; and (d) treating the subject with one or more treatment modalities appropriate for a subject having or likely to develop aggressive thyroid cancer. Similar approaches are applied to other human cancers harboring both BRAF V600E mutation and TERT promoter mutations.