Q (sonnet-5.5): show me a histogram of C228T mutations in the tert promoter across cancer types

▶ read_guide
{
 "uri": "cbioportal://mutation-frequency-guide"
}

◀ result
# Mutation Frequency Analysis Guide

## IMPORTANT: Reporting Mutation Frequencies
- **ALWAYS report frequencies as percentages**, not raw counts: `frequency = (altered_samples / total_profiled_samples) × 100`
- For quick frequency lookups, **prefer the TCGA Pan-Cancer Atlas study first**, then offer to expand to other studies
- When reporting across multiple studies, show **ranges** (e.g., "TP53 is mutated in 30–60% of samples") rather than a single average
- **NEVER** sum mutation events across studies to compute an aggregate frequency — this can exceed 100% due to double-counting
- Warn users that samples may overlap across cohorts (e.g., MSK studies may share patients)
- **Choose and state the counting unit**: use patient-level frequencies for prevalence/rate questions unless the user explicitly asks for samples; use sample-level frequencies when the user asks about samples.
- **For "across cancer types" questions**, jump to the [Cross-Cancer-Type Mutation Frequency](#cross-cancer-type-mutation-frequency) section below — there is one correct recipe and several common wrong ones.

## Counting Unit: Samples vs Patients

Before answering any mutation count or frequency question, decide whether the unit is samples or patients and state that choice in the answer.

| User wording | Counting unit |
|--------------|---------------|
| "prevalence", "rate", "fraction of patients", "patients with", "how common is" | Patient-level: `COUNT(DISTINCT patient_unique_id)` |
| "samples", "specimens", "biopsies", sample-level cohort composition | Sample-level: `COUNT(DISTINCT sample_unique_id)` |
| Ambiguous | Ask, or default to patient-level for prevalence/rate language and say so |

### Cross-study sample-count caveat

When an answer touches more than one study and reports a sample count, prepend a one-line caveat:

> Sample IDs are unique within cBioPortal study prefixes, not guaranteed biological-sample identifiers across studies; overlapping cohorts can count the same patient/sample more than once.

Prefer one of these safer approaches:

- Use a shipped `cancer_study_query_preferences` cohort such as `pan_cancer_tcga` or `all_studies_non_redundant`.
- Restrict to one named study.
- Aggregate by `patient_unique_id` when the biological question is patient prevalence.

## STOP rule: a frequency above 100% means your query is wrong

If your query returns a frequency over 100%, **do not try to debug or explain the data inconsistency to the user**. The cause is always one of these query bugs:

- Summing mutation events instead of `COUNT(DISTINCT sample_unique_id)` for the numerator
- Using a study-wide sample count as the denominator instead of the gene-specific profiled count
- Cross-study aggregation where the same biological sample appears under multiple `sample_unique_id` values (e.g., MSK-IMPACT and MSK-CHORD share patients)
- **Joining the profiled CTE through `gene_panel` / `gene_panel_list` without a WES branch.** `gene_panel_id = 'WES'` is *not* a row in … (36467 more chars)

▶ read_guide
{
 "uri": "cbioportal://common-pitfalls#16"
}

◀ result
### 16. 🚨 SILENT QUERY SUBSTITUTION ("did you mean...")

When the user's wording differs from canonical terminology (e.g. "V600V" looks like "V600E" with a typo, or "point mutation" sounds like "missense"), it is forbidden to silently rewrite the question and answer the rewritten version. Doing so produces an answer that looks confident but is for a different question — the user cannot tell what was changed.

#### ❌ Wrong: silently substitute

> User: *"Find patients in colorectal cancer with the V600V alteration in BRAF"*
> Agent: *(internally treats this as V600E)* "I found 412 samples with BRAF V600E in colorectal studies..."

> User: *"What is the most prevalent TP53 mutation in uterine cancer that is not a point mutation?"*
> Agent: *(internally treats "point mutation" = "missense", silently excludes only missense)* "The most prevalent non-missense TP53 mutation is..."

#### ✅ Correct: answer the literal question, flag any normalization

For an unusual-looking variant the user may have typed deliberately:
- Query for what was asked, literally.
- If 0 rows come back, **explain *why* zero is the expected answer** before suggesting a likely-intended alternative. For synonymous variants (e.g. BRAF V600V, TP53 R175R), the explanation is: *cBioPortal's mutation tables filter out synonymous (silent) variants in most studies, so 0 hits means "filtered upstream", not "no such variant exists in any patient"*. Then ask: *"Did you mean V600E (the canonical activating variant)? Or would you like me to look for V600V in the studies that do retain synonymous calls?"*
- If the wording is ambiguous (e.g. "point mutation"), ask the user which definition they meant before querying — do not pick one silently.

#### Mutation-type terminology mapping (use this to disambiguate)

| User says | Canonical definition | `mutation_type` filter |
|---|---|---|
| "point mutation" | Any SNV (single-nucleotide variant) — includes missense, nonsense, synonymous, splice-site SNVs | `mutation_type IN ('Missense_Mutation','Nonsense_Mutation','Silent','Splice_Site')` — **but ask the user to confirm scope first** |
| "missense" | Single amino-acid substitution that changes the protein | `mutation_type = 'Missense_Mutation'` |
| "nonsense" / "stop-gain" | Premature stop codon | `mutation_type = 'Nonsense_Mutation'` |
| "synonymous" / "silent" | Nucleotide change with no amino-acid change | `mutation_type = 'Silent'` (**often filtered out of public datasets** — see below) |
| "splice site" | Mutation in canonical splice acceptor/donor | `mutation_type = 'Splice_Site'` |
| "frameshift" | Indel changing reading frame | `mutation_type IN ('Frame_Shift_Ins','Frame_Shift_Del')` |
| "indel" / "in-frame" | In-frame insertion or deletion | `mutation_type IN ('In_Frame_Ins','In_Frame_Del')` |
| "truncating" | Anything that disrupts the protein early | `mutation_type IN ('Nonsense_Mutation','Frame_Shift_Ins','Frame_Shift_Del','Splice_Site','Nonstop_Mutation')` |

**Synonymous-variant filter. … (785 more chars)

▶ clickhouse_list_table_columns
{
 "table": "genomic_event_derived"
}

◀ result
{"columns":[{"name":"sample_unique_id","type":"String"},{"name":"hugo_gene_symbol","type":"String","comment":"HUGO gene symbol (e.g., TP53, KRAS, BRAF). Use for gene-specific queries."},{"name":"entrez_gene_id","type":"Int32"},{"name":"gene_panel_stable_id","type":"LowCardinality(String)"},{"name":"cancer_study_identifier","type":"LowCardinality(String)"},{"name":"genetic_profile_stable_id","type":"LowCardinality(String)"},{"name":"variant_type","type":"LowCardinality(String)","comment":"Type of genomic event: \"mutation\" for SNVs/indels, \"cna\" for copy number alterations, \"structural_variant\" for SVs. Always filter by this."},{"name":"mutation_variant","type":"String","comment":"Protein change notation (e.g., p.V600E, p.R175H). Use for specific variant queries. \"NA\" for non-mutation events."},{"name":"mutation_type","type":"LowCardinality(String)"},{"name":"mutation_status","type":"LowCardinality(String)","comment":"For mutations: Somatic, Germline, UNKNOWN, or UNCALLED. Filter mutation_status != \"UNCALLED\" to exclude uncertain calls. Include all other statuses."},{"name":"driver_filter","type":"LowCardinality(String)"},{"name":"driver_filter_annotation","type":"String"},{"name":"driver_tiers_filter","type":"LowCardinality(String)"},{"name":"driver_tiers_filter_annotation","type":"String"},{"name":"cna_alteration","type":"Nullable(Int8)","comment":"Copy number alteration: only 2 = amplification (AMP) and -2 = deep deletion (HOMDEL) are stored. Shallow deletion (-1), diploid (0) and gain (1) are not in this table; query genetic_alteration_derived WHERE profile_type = 'gistic' (alteration_value is a String, e.g. '-1'). NULL for non-CNA events."},{"name":"cna_cytoband","type":"String"},{"name":"sv_event_info","type":"String"},{"name":"patient_unique_id","type":"String"},{"name":"off_panel","type":"Bool","comment":"Boolean: 1 = mutation outside gene panel coverage (off-panel), 0 = within panel (on-panel). Filter off_panel = 0 for reliable frequency calculations."}]}

▶ clickhouse_run_select_query
{
 "query": "SELECT mutation_type, mutation_variant, count() n, uniqExact(sample_unique_id) s FROM genomic_event_derived WHERE hugo_gene_symbol='TERT' AND variant_type='mutation' AND (mutation_type IN ('5''Flank','Promoter','5''UTR','Upstream') OR mutation_variant ILIKE '%228%' OR mutation_variant ILIKE '%124%' OR mutation_variant ILIKE '%C250%' OR mutation_variant ILIKE '%promoter%') GROUP BY mutation_type, mutation_variant ORDER BY n DESC LIMIT 30"
}

◀ result
{"rows":[{"mutation_type":"5'Flank","mutation_variant":"Promoter","n":19590,"s":18946},{"mutation_type":"Missense_Mutation","mutation_variant":"A228V","n":7,"s":7},{"mutation_type":"Missense_Mutation","mutation_variant":"A228D","n":5,"s":5},{"mutation_type":"Missense_Mutation","mutation_variant":"P1124S","n":4,"s":4},{"mutation_type":"Missense_Mutation","mutation_variant":"P1124L","n":3,"s":3},{"mutation_type":"Missense_Mutation","mutation_variant":"P124S","n":2,"s":2},{"mutation_type":"Missense_Mutation","mutation_variant":"P1124H","n":1,"s":1}]}

▶ clickhouse_list_tables
{}

◀ result
{"tables":[{"name":"allele_specific_copy_number"},{"name":"alteration_driver_annotation"},{"name":"cancer_study"},{"name":"cancer_study_query_preferences"},{"name":"cancer_study_tags"},{"name":"cbioportal_sequence_state"},{"name":"clinical_attribute_counts"},{"name":"clinical_attribute_meta"},{"name":"clinical_data_derived"},{"name":"clinical_event"},{"name":"clinical_event_data"},{"name":"clinical_event_data_derived"},{"name":"clinical_event_derived"},{"name":"clinical_patient"},{"name":"clinical_sample"},{"name":"cna_event"},{"name":"cna_panel_gene_coverage"},{"name":"cna_wes_coverage"},{"name":"co_altered_genes_in_study"},{"name":"copy_number_seg"},{"name":"copy_number_seg_file"},{"name":"gene"},{"name":"gene_alias"},{"name":"gene_alteration_frequency_by_cancer_type"},{"name":"gene_cna_distribution_in_study"},{"name":"gene_mutation_frequency_by_cancer_type"},{"name":"gene_mutation_frequency_in_studies"},{"name":"gene_mutation_frequency_in_study"},{"name":"gene_mutation_variants_in_study"},{"name":"gene_pair_coexpression"},{"name":"gene_panel"},{"name":"gene_panel_list"},{"name":"gene_panel_to_gene_derived"},{"name":"generic_assay_data_derived"},{"name":"generic_assay_meta_derived"},{"name":"generic_assay_profile_entity_derived"},{"name":"generic_entity_properties"},{"name":"geneset"},{"name":"geneset_gene"},{"name":"geneset_hierarchy_leaf"},{"name":"geneset_hierarchy_node"},{"name":"genetic_alteration"},{"name":"genetic_alteration_derived"},{"name":"genetic_entity"},{"name":"genetic_profile"},{"name":"genetic_profile_link"},{"name":"genetic_profile_samples"},{"name":"genomic_event_derived"},{"name":"gistic"},{"name":"gistic_to_gene"},{"name":"info"},{"name":"mut_sig"},{"name":"mutation"},{"name":"mutation_count_by_keyword"},{"name":"mutation_derived"},{"name":"mutation_event"},{"name":"mutation_panel_gene_coverage"},{"name":"mutation_wes_coverage"},{"name":"patient"},{"name":"reference_genome"},{"name":"reference_genome_gene"},{"name":"resource_definition"},{"name":"resource_patient"},{"name":"resource_sample"},{"name":"resource_study"},{"name":"sample"},{"name":"sample_cna_event"},{"name":"sample_derived"},{"name":"sample_list"},{"name":"sample_list_list"},{"name":"sample_profile"},{"name":"sample_to_gene_panel_derived"},{"name":"structural_variant"},{"name":"sv_panel_gene_coverage"},{"name":"sv_wes_coverage"},{"name":"top_cna_genes_in_study"},{"name":"top_mutated_genes_in_cohort"},{"name":"top_mutated_genes_in_study"},{"name":"top_sv_genes_in_study"},{"name":"treatment_counts_in_study"},{"name":"treatment_regimens_in_study"},{"name":"type_of_cancer"}]}

▶ clickhouse_list_table_columns
{
 "table": "mutation_derived"
}

◀ result
{"columns":[{"name":"molecularProfileId","type":"String","comment":"Stable ID of the genetic profile"},{"name":"sampleId","type":"String","comment":"Stable ID of the sample"},{"name":"sampleInternalId","type":"Int64"},{"name":"patientId","type":"String","comment":"Stable ID of the patient"},{"name":"entrezGeneId","type":"Int64","comment":"Entrez Gene ID from mutation table (NOT NULL)"},{"name":"studyId","type":"String","comment":"Cancer study identifier"},{"name":"center","type":"Nullable(String)","comment":"Sequencing center"},{"name":"mutationStatus","type":"Nullable(String)","comment":"Mutation status (e.g., Somatic, Germline)"},{"name":"validationStatus","type":"Nullable(String)","comment":"Validation status"},{"name":"tumorAltCount","type":"Nullable(Int64)","comment":"Tumor alternate allele count"},{"name":"tumorRefCount","type":"Nullable(Int64)","comment":"Tumor reference allele count"},{"name":"normalAltCount","type":"Nullable(Int64)","comment":"Normal alternate allele count"},{"name":"normalRefCount","type":"Nullable(Int64)","comment":"Normal reference allele count"},{"name":"aminoAcidChange","type":"Nullable(String)","comment":"Amino acid change"},{"name":"chr","type":"Nullable(String)","comment":"Chromosome"},{"name":"startPosition","type":"Nullable(Int64)","comment":"Start position"},{"name":"endPosition","type":"Nullable(Int64)","comment":"End position"},{"name":"referenceAllele","type":"Nullable(String)","comment":"Reference allele"},{"name":"tumorSeqAllele","type":"Nullable(String)","comment":"Tumor sequence allele"},{"name":"proteinChange","type":"Nullable(String)","comment":"Protein change"},{"name":"mutationType","type":"Nullable(String)","comment":"Type of mutation"},{"name":"ncbiBuild","type":"Nullable(String)","comment":"NCBI build version"},{"name":"variantType","type":"Nullable(String)","comment":"Variant type"},{"name":"refseqMrnaId","type":"Nullable(String)","comment":"RefSeq mRNA ID"},{"name":"proteinPosStart","type":"Nullable(Int64)","comment":"Protein position start"},{"name":"proteinPosEnd","type":"Nullable(Int64)","comment":"Protein position end"},{"name":"keyword","type":"Nullable(String)","comment":"Keyword"},{"name":"annotationJSON","type":"Nullable(String)","comment":"Annotation JSON"},{"name":"driverFilter","type":"Nullable(String)","comment":"Driver filter"},{"name":"driverFilterAnnotation","type":"Nullable(String)","comment":"Driver filter annotation"},{"name":"driverTiersFilter","type":"Nullable(String)","comment":"Driver tiers filter"},{"name":"driverTiersFilterAnnotation","type":"Nullable(String)","comment":"Driver tiers filter annotation"},{"name":"GENE.entrezGeneId","type":"Nullable(Int64)","comment":"Gene entrez ID"},{"name":"GENE.hugoGeneSymbol","type":"Nullable(String)","comment":"HUGO gene symbol"},{"name":"GENE.type","type":"Nullable(String)","comment":"Gene type"},{"name":"alleleSpecificCopyNumber.ascnIntegerCopyNumber","type":"Nullable(Int64)","comment":"ASCN integer copy number"},{"name":"alleleSpe … (756 more chars)

▶ clickhouse_run_select_query
{
 "query": "SELECT ncbiBuild, startPosition, referenceAllele, tumorSeqAllele, count() n, uniqExact(studyId) studies FROM mutation_derived WHERE `GENE.hugoGeneSymbol`='TERT' AND mutationType='5''Flank' AND startPosition BETWEEN 1295100 AND 1295260 GROUP BY ALL ORDER BY n DESC LIMIT 20"
}

◀ result
{"rows":[{"ncbiBuild":"GRCh37","startPosition":1295228,"referenceAllele":"G","tumorSeqAllele":"A","n":13001,"studies":113},{"ncbiBuild":"GRCh37","startPosition":1295250,"referenceAllele":"G","tumorSeqAllele":"A","n":3136,"studies":84},{"ncbiBuild":"GRCh37","startPosition":1295250,"referenceAllele":"GAGGG","tumorSeqAllele":"AAGGA","n":691,"studies":30},{"ncbiBuild":"GRCh38","startPosition":1295113,"referenceAllele":"G","tumorSeqAllele":"A","n":266,"studies":3},{"ncbiBuild":"GRCh37","startPosition":1295242,"referenceAllele":"GG","tumorSeqAllele":"AA","n":265,"studies":24},{"ncbiBuild":"GRCh37","startPosition":1295228,"referenceAllele":"G","tumorSeqAllele":"T","n":226,"studies":36},{"ncbiBuild":"GRCh37","startPosition":1295228,"referenceAllele":"GG","tumorSeqAllele":"AA","n":191,"studies":17},{"ncbiBuild":"GRCh37","startPosition":1295205,"referenceAllele":"G","tumorSeqAllele":"A","n":91,"studies":9},{"ncbiBuild":"GRCh38","startPosition":1295135,"referenceAllele":"G","tumorSeqAllele":"A","n":81,"studies":3},{"ncbiBuild":"GRCh37","startPosition":1295230,"referenceAllele":"G","tumorSeqAllele":"A","n":40,"studies":7},{"ncbiBuild":"GRCh37","startPosition":1295253,"referenceAllele":"G","tumorSeqAllele":"A","n":32,"studies":11},{"ncbiBuild":"GRCh37","startPosition":1295204,"referenceAllele":"G","tumorSeqAllele":"A","n":29,"studies":5},{"ncbiBuild":"GRCh37","startPosition":1295242,"referenceAllele":"G","tumorSeqAllele":"A","n":28,"studies":10},{"ncbiBuild":"GRCh37","startPosition":1295250,"referenceAllele":"GAGG","tumorSeqAllele":"AAGA","n":26,"studies":5},{"ncbiBuild":"GRCh37","startPosition":1295243,"referenceAllele":"G","tumorSeqAllele":"A","n":25,"studies":10},{"ncbiBuild":"GRCh37","startPosition":1295228,"referenceAllele":"GGG","tumorSeqAllele":"AGA","n":18,"studies":6},{"ncbiBuild":"GRCh37","startPosition":1295217,"referenceAllele":"G","tumorSeqAllele":"A","n":17,"studies":7},{"ncbiBuild":"GRCh37","startPosition":1295201,"referenceAllele":"G","tumorSeqAllele":"A","n":16,"studies":6},{"ncbiBuild":"GRCh37","startPosition":1295176,"referenceAllele":"G","tumorSeqAllele":"A","n":14,"studies":4},{"ncbiBuild":"GRCh37","startPosition":1295176,"referenceAllele":"G","tumorSeqAllele":"C","n":13,"studies":6}]}

▶ clickhouse_run_select_query
{
 "query": "WITH cohort AS (SELECT cancer_study_identifier FROM cancer_study_query_preferences WHERE preference_name='large_genomic_cohort'),
sct AS (SELECT cd.sample_unique_id AS sample_unique_id, cd.attribute_value AS cancer_type FROM clinical_data_derived cd WHERE cd.cancer_study_identifier IN (SELECT cancer_study_identifier FROM cohort) AND cd.attribute_name='CANCER_TYPE'),
alt AS (SELECT sct.cancer_type AS cancer_type, uniqExact(m.sample_unique_id) altered FROM (SELECT concat(studyId,'_',sampleId) AS sample_unique_id FROM mutation_derived WHERE studyId IN (SELECT cancer_study_identifier FROM cohort) AND `GENE.hugoGeneSymbol`='TERT' AND ((ncbiBuild='GRCh37' AND startPosition=1295228) OR (ncbiBuild='GRCh38' AND startPosition=1295113)) AND referenceAllele='G' AND tumorSeqAllele='A' AND ifNull(mutationStatus,'')!='UNCALLED') m JOIN sct USING sample_unique_id GROUP BY cancer_type),
prof AS (SELECT sct.cancer_type AS cancer_type, uniqExact(p.sample_unique_id) profiled FROM (SELECT sample_unique_id FROM mutation_panel_gene_coverage WHERE hugo_gene_symbol='TERT' AND cancer_study_identifier IN (SELECT cancer_study_identifier FROM cohort) UNION ALL SELECT sample_unique_id FROM mutation_wes_coverage WHERE cancer_study_identifier IN (SELECT cancer_study_identifier FROM cohort)) p JOIN sct USING sample_unique_id GROUP BY cancer_type)
SELECT prof.cancer_type, ifNull(alt.altered,0) altered, prof.profiled, round(ifNull(alt.altered,0)*100/prof.profiled,1) pct FROM prof LEFT JOIN alt USING cancer_type WHERE prof.profiled>=50 ORDER BY altered DESC",
 "max_rows": 100
}

◀ result
{"rows":[{"cancer_type":"Bladder Cancer","altered":1453,"profiled":2526,"pct":57.5},{"cancer_type":"Glioma","altered":1151,"profiled":2322,"pct":49.6},{"cancer_type":"Thyroid Cancer","altered":417,"profiled":867,"pct":48.1},{"cancer_type":"Melanoma","altered":414,"profiled":1831,"pct":22.6},{"cancer_type":"Hepatobiliary Cancer","altered":196,"profiled":1431,"pct":13.7},{"cancer_type":"Soft Tissue Sarcoma","altered":150,"profiled":2307,"pct":6.5},{"cancer_type":"Head and Neck Cancer","altered":135,"profiled":657,"pct":20.5},{"cancer_type":"Cancer of Unknown Primary","altered":118,"profiled":1581,"pct":7.5},{"cancer_type":"Non-Small Cell Lung Cancer","altered":109,"profiled":7867,"pct":1.4},{"cancer_type":"Renal Cell Carcinoma","altered":94,"profiled":1209,"pct":7.8},{"cancer_type":"Skin Cancer, Non-Melanoma","altered":47,"profiled":455,"pct":10.3},{"cancer_type":"Ovarian Cancer","altered":38,"profiled":2140,"pct":1.8},{"cancer_type":"Colorectal Cancer","altered":35,"profiled":5277,"pct":0.7},{"cancer_type":"Sex Cord Stromal Tumor","altered":30,"profiled":91,"pct":33},{"cancer_type":"Breast Cancer","altered":25,"profiled":6807,"pct":0.4},{"cancer_type":"Salivary Gland Cancer","altered":24,"profiled":411,"pct":5.8},{"cancer_type":"Endometrial Cancer","altered":24,"profiled":2445,"pct":1},{"cancer_type":"Bone Cancer","altered":23,"profiled":590,"pct":3.9},{"cancer_type":"Cervical Cancer","altered":20,"profiled":351,"pct":5.7},{"cancer_type":"Mesothelioma","altered":19,"profiled":408,"pct":4.7},{"cancer_type":"Vaginal Cancer","altered":14,"profiled":57,"pct":24.6},{"cancer_type":"Embryonal Tumor","altered":11,"profiled":80,"pct":13.8},{"cancer_type":"Uterine Sarcoma","altered":9,"profiled":344,"pct":2.6},{"cancer_type":"Pancreatic Cancer","altered":9,"profiled":2851,"pct":0.3},{"cancer_type":"Prostate Cancer","altered":6,"profiled":3324,"pct":0.2},{"cancer_type":"CNS Cancer","altered":6,"profiled":170,"pct":3.5},{"cancer_type":"Peripheral Nervous System","altered":5,"profiled":411,"pct":1.2},{"cancer_type":"Esophagogastric Cancer","altered":5,"profiled":1834,"pct":0.3},{"cancer_type":"Miscellaneous Brain Tumor","altered":4,"profiled":58,"pct":6.9},{"cancer_type":"Small Cell Lung Cancer","altered":4,"profiled":466,"pct":0.9},{"cancer_type":"Ampullary Cancer","altered":4,"profiled":134,"pct":3},{"cancer_type":"Adrenocortical Carcinoma","altered":4,"profiled":88,"pct":4.5},{"cancer_type":"Gastrointestinal Stromal Tumor","altered":3,"profiled":635,"pct":0.5},{"cancer_type":"Small Bowel Cancer","altered":3,"profiled":161,"pct":1.9},{"altered":2,"profiled":50,"pct":4},{"cancer_type":"Wilms Tumor","altered":2,"profiled":68,"pct":2.9},{"cancer_type":"Nerve Sheath Tumor","altered":2,"profiled":142,"pct":1.4},{"cancer_type":"Anal Cancer","altered":2,"profiled":143,"pct":1.4},{"cancer_type":"Gastrointestinal Neuroendocrine Tumor","altered":2,"profiled":210,"pct":1},{"cancer_type":"Germ Cell Tumor","altered":1,"profiled":725,"pct":0.1},{"cancer_type":"Sellar Tumo … (244 more chars)

▶ resolve_and_route
{
 "studyIds": [
  "msk_impact_50k_2026"
 ]
}

◀ result
{"success":true,"message":"Found 1 study. Use the metadata to call the appropriate navigation tool(s).","data":{"totalCount":1,"studiesWithMetadata":[{"studyId":"msk_impact_50k_2026","name":"MSK-IMPACT 50K Clinical Sequencing Cohort (MSK, Cancer Cell 2026)","sampleCount":54331,"studyViewUrl":"https://www.cbioportal.org/study?id=msk_impact_50k_2026","metadata":{"clinicalAttributeIds":["AGE_AT_DX","ANCESTRY_LABEL","CANCER_TYPE","CANCER_TYPE_DETAILED","DISEASE_STATUS","FACETS_PLOIDY","FACETS_PURITY","FACETS_QC","FACETS_SUITE_VERSION","FACETS_WGD","FRACTION_GENOME_ALTERED","GENE_PANEL","HLA-A1","HLA-A2","HLA-B1","HLA-B2","HLA-C1","HLA-C2","HLA_A1_LOH","HLA_A2_LOH","HLA_B1_LOH","HLA_B2_LOH","HLA_C1_LOH","HLA_C2_LOH","HLA_GENOTYPE_AVAILABLE","METASTATIC_SITE","MSI_SCORE","MSI_TYPE","MUTATION_COUNT","N_OTHER_CANCER_TYPES","ONCOTREE_CODE","OS_MONTHS","OS_STATUS","PRIMARY_SITE","PURITY_ESTIMATE_FROM_MUTATIONS","SAMPLE_COUNT","SAMPLE_COVERAGE","SAMPLE_TYPE","SEX","SOMATIC_STATUS","TMB_SCORE","TUMOR_PURITY"],"molecularProfileIds":["msk_impact_50k_2026_gistic","msk_impact_50k_2026_mutations","msk_impact_50k_2026_structural_variants"],"genericAssayProfiles":["msk_impact_50k_2026_armlevel_cna","msk_impact_50k_2026_loh_hla","msk_impact_50k_2026_mutational_signatures_contribution_v2"],"availableComparisonTabs":["overlap","clinical","survival","alterations","mutations","generic_assay_armlevel_cna","generic_assay_loh_hla","generic_assay_mutational_signature"]}}]}}

▶ navigate_to_results_view
{
 "studyIds": [
  "msk_impact_50k_2026"
 ],
 "genes": [
  "TERT: MUT = PROMOTER"
 ],
 "tab": "cancerTypesSummary"
}

◀ result
{"success":true,"message":"Navigating to https://www.cbioportal.org/results/cancerTypesSummary?cancer_study_list=msk_impact_50k_2026&gene_list=TERT%3A+MUT+%3D+PROMOTER&case_set_id=msk_impact_50k_2026_all","url":"https://www.cbioportal.org/results/cancerTypesSummary?cancer_study_list=msk_impact_50k_2026&gene_list=TERT%3A+MUT+%3D+PROMOTER&case_set_id=msk_impact_50k_2026_all","data":{"studyIds":["msk_impact_50k_2026"],"studies":[{"studyId":"msk_impact_50k_2026","name":"MSK-IMPACT 50K Clinical Sequencing Cohort (MSK, Cancer Cell 2026)","sampleCount":54331}],"genes":["TERT"],"caseSetId":"msk_impact_50k_2026_all","pageDescription":"Alteration frequencies for queried genes by cancer type."}}

═ answer (success)
## TERT promoter C228T by cancer type

I used the MSK-IMPACT 50K cohort (`msk_impact_50k_2026`) and counted samples. I picked it because its targeted panels cover the TERT promoter, whereas the exome-based TCGA data covers it poorly. The database doesn't label variants as C228T, so I identified them by position. I counted only the G>A change at chr5:1,295,228 (GRCh37) or chr5:1,295,113 (GRCh38), which is C228T on the gene's coding strand. C250T and other promoter variants are excluded.

Types with at least 50 profiled samples, sorted by frequency (each █ is about 2.5%):

| Cancer type | C228T / profiled | % | |
|---|---|---|---|
| Bladder Cancer | 1,453 / 2,526 | 57.5 | ██████████████████████▉ |
| Glioma | 1,151 / 2,322 | 49.6 | ███████████████████▊ |
| Thyroid Cancer | 417 / 867 | 48.1 | ███████████████████▏ |
| Sex Cord Stromal Tumor | 30 / 91 | 33.0 | █████████████▏ |
| Vaginal Cancer | 14 / 57 | 24.6 | █████████▊ |
| Melanoma | 414 / 1,831 | 22.6 | █████████ |
| Head and Neck Cancer | 135 / 657 | 20.5 | ████████▏ |
| Hepatobiliary Cancer | 196 / 1,431 | 13.7 | █████▌ |
| Embryonal Tumor | 11 / 80 | 13.8 | █████▌ |
| Skin Cancer, Non-Melanoma | 47 / 455 | 10.3 | ████▏ |
| Renal Cell Carcinoma | 94 / 1,209 | 7.8 | ███ |
| Cancer of Unknown Primary | 118 / 1,581 | 7.5 | ███ |
| Miscellaneous Brain Tumor | 4 / 58 | 6.9 | ██▊ |
| Soft Tissue Sarcoma | 150 / 2,307 | 6.5 | ██▌ |
| Salivary Gland Cancer | 24 / 411 | 5.8 | ██▎ |
| Cervical Cancer | 20 / 351 | 5.7 | ██▎ |
| Mesothelioma | 19 / 408 | 4.7 | █▉ |
| Adrenocortical Carcinoma | 4 / 88 | 4.5 | █▊ |
| Bone Cancer | 23 / 590 | 3.9 | █▌ |
| CNS Cancer | 6 / 170 | 3.5 | █▍ |
| Ampullary Cancer | 4 / 134 | 3.0 | █▏ |
| Wilms Tumor | 2 / 68 | 2.9 | █▏ |
| Uterine Sarcoma | 9 / 344 | 2.6 | █ |
| Small Bowel Cancer | 3 / 161 | 1.9 | ▊ |
| Ovarian Cancer | 38 / 2,140 | 1.8 | ▋ |
| Non-Small Cell Lung Cancer | 109 / 7,867 | 1.4 | ▌ |
| Nerve Sheath Tumor | 2 / 142 | 1.4 | ▌ |
| Anal Cancer | 2 / 143 | 1.4 | ▌ |
| Peripheral Nervous System | 5 / 411 | 1.2 | ▌ |
| Endometrial Cancer | 24 / 2,445 | 1.0 | ▍ |
| Gastrointestinal Neuroendocrine Tumor | 2 / 210 | 1.0 | ▍ |
| Small Cell Lung Cancer | 4 / 466 | 0.9 | ▎ |
| Colorectal Cancer | 35 / 5,277 | 0.7 | ▎ |
| Gastrointestinal Stromal Tumor | 3 / 635 | 0.5 | ▏ |
| Breast Cancer | 25 / 6,807 | 0.4 | ▏ |
| Pancreatic Cancer | 9 / 2,851 | 0.3 | ▏ |
| Esophagogastric Cancer | 5 / 1,834 | 0.3 | ▏ |
| Prostate Cancer | 6 / 3,324 | 0.2 | ▏ |
| Germ Cell Tumor | 1 / 725 | 0.1 | ▏ |
| Sellar Tumor, Appendiceal, Retinoblastoma, Thymic | 0 | 0 | |

One group with no cancer-type label (2 / 50) is left out of the table.

**Caveats**
- The "profiled" counts include every sample run on a panel that lists TERT. Some older panels may not actually cover the promoter, so the true frequencies could be somewhat higher.
- Small groups (for example Vaginal Cancer, n=57) give unstable percentages.
- Cancer type labels are as recorded in this one cohort. Other studies may label or split them differently.

[View TERT promoter alteration frequency by cancer type in cBioPortal](https://www.cbioportal.org/results/cancerTypesSummary?cancer_study_list=msk_impact_50k_2026&gene_list=TERT%3A+MUT+%3D+PROMOTER&case_set_id=msk_impact_50k_2026_all)

That link opens cBioPortal's own bar chart of promoter-mutation frequency by cancer type. It counts all TERT promoter mutations, so it includes C250T and other variants. You can also open the [MSK-IMPACT 50K study overview](https://www.cbioportal.org/study?id=msk_impact_50k_2026).