Understanding Your Genomic Test Results
What These Results Mean
Your genomic testing shows a TERT promoter mutation (C228T), microsatellite stable (MSS) status, and low tumor mutational burden (TMB of 4.7 mutations/Mb), which indicates your tumor is unlikely to respond to standard immunotherapy but may have specific treatment implications depending on your cancer type. 1
Key Findings Explained
TERT Promoter Mutation C228T
- TERT promoter mutations regulate telomerase activity, which is highly associated with cancer development and progression 1
- The C228T mutation specifically has been associated with increased risk of tumor recurrence and death in certain cancers, particularly head and neck cancers 2
- TERT mutations are found in approximately 36% of HBV-related hepatocellular carcinoma cases and are considered a driver of carcinogenesis 1
- In melanoma, TERT promoter mutations are under investigation for diagnostic and prognostic value, though routine testing is not yet recommended outside of clinical trials 1
Microsatellite Stable (MSS) Status
- MSS tumors typically do not respond well to immune checkpoint inhibitors (anti-PD-1/PD-L1 therapies) 1, 3
- Approximately 95% of colorectal cancers are MSS, and these generally require different treatment approaches than MSI-high tumors 4
- MSS status indicates your mismatch repair system is functioning normally 3
Low Tumor Mutational Burden (4.7 Mutations/Mb)
- TMB below 10 mutations/Mb is considered low and predicts poor response to immunotherapy 1, 5
- The FDA-approved threshold for TMB-high is ≥10 mutations/Mb, and your result of 4.7 is well below this cutoff 1
- Low TMB is typical for most solid tumors and correlates with the MSS status 4, 6
No Mutations in BRAF, NF1, or NRAS
- The absence of these common driver mutations means standard targeted therapies directed at these pathways are not appropriate for your tumor 1
- This information helps guide away from ineffective treatments 1
Treatment Implications
Immunotherapy Considerations
- Standard immune checkpoint inhibitors (pembrolizumab, nivolumab) are NOT recommended based on your MSS status and low TMB 1, 5
- Only 2.9% of MSS colorectal cancers have high TMB that might respond to immunotherapy, and your tumor does not fall into this category 4
- Rare case reports exist of MSS/low TMB tumors responding to combined stereotactic radiotherapy plus immunotherapy, but this remains investigational 3
Standard Treatment Approach
- Your treatment should focus on conventional therapies appropriate for your specific cancer type (surgery, chemotherapy, radiation) rather than immunotherapy 1
- The TERT mutation alone does not currently have FDA-approved targeted therapies available 1
- Molecular tumor board discussion may be valuable to explore clinical trial options or off-label therapies 1
Clinical Context
Prognostic Significance
- The TERT C228T mutation may indicate more aggressive disease behavior with higher recurrence risk 2
- In head and neck cancer specifically, C228T mutation was associated with significantly decreased disease-free survival (20.0% vs 63.0%) and overall survival (16.7% vs 45.1%) 2
- The combination of TERT mutation with other genomic features may influence prognosis depending on your primary cancer type 1, 7
Next Steps
- Discuss with your oncologist whether additional molecular testing might identify other actionable targets (such as NTRK fusions, MET fusions, FGFR alterations, or RET fusions) 1, 7
- Consider enrollment in clinical trials, particularly those investigating novel therapies for tumors with TERT mutations 1
- Ensure your case is reviewed by a molecular tumor board if available at your institution, as complex genomic profiles benefit from multidisciplinary expertise 1