Q (sonnet): What percentage of patients in the MSK-CHORD Study have at least one TP53 mutation?

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

▶ list_studies
{
 "search": "MSK CHORD"
}

◀ 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 … (35166 more chars)

◀ result
{"result":[{"cancer_study_identifier":"msk_chord_2024","name":"MSK-CHORD (MSK, Nature 2024)","type_of_cancer_id":"mixed","sample_count":25040,"has_guide":true,"url":"https://www.cbioportal.org/study/summary?id=msk_chord_2024"}]}

▶ clickhouse_run_select_query
{
 "query": "SELECT * FROM gene_mutation_frequency_in_study(study = 'msk_chord_2024', gene = 'TP53') ORDER BY frequency_pct DESC"
}

◀ result
{"rows":[{"cancer_type":"Colorectal Cancer","altered_samples":4068,"profiled_samples":5543,"frequency_pct":73.4},{"cancer_type":"Pancreatic Cancer","altered_samples":2076,"profiled_samples":3109,"frequency_pct":66.8},{"cancer_type":"Non-Small Cell Lung Cancer","altered_samples":4005,"profiled_samples":7809,"frequency_pct":51.3},{"cancer_type":"Breast Cancer","altered_samples":2138,"profiled_samples":5368,"frequency_pct":39.8},{"cancer_type":"Prostate Cancer","altered_samples":837,"profiled_samples":3211,"frequency_pct":26.1}]}

▶ clickhouse_run_select_query
{
 "query": "
WITH profiled_patients AS (
    SELECT DISTINCT c.patient_unique_id
    FROM sample_to_gene_panel_derived s
    JOIN (SELECT DISTINCT sample_unique_id, patient_unique_id FROM clinical_data_derived
          WHERE cancer_study_identifier = 'msk_chord_2024') c USING (sample_unique_id)
    WHERE s.cancer_study_identifier = 'msk_chord_2024' AND s.alteration_type = 'MUTATION_EXTENDED'
),
altered_patients AS (
    SELECT DISTINCT c.patient_unique_id
    FROM genomic_event_derived g
    JOIN (SELECT DISTINCT sample_unique_id, patient_unique_id FROM clinical_data_derived
          WHERE cancer_study_identifier = 'msk_chord_2024') c USING (sample_unique_id)
    WHERE g.cancer_study_identifier = 'msk_chord_2024'
      AND g.variant_type = 'mutation'
      AND g.mutation_status != 'UNCALLED'
      AND g.hugo_gene_symbol = 'TP53'
      AND g.off_panel = 0
)
SELECT
    (SELECT count() FROM profiled_patients) AS profiled_patients,
    (SELECT count() FROM altered_patients WHERE patient_unique_id IN (SELECT patient_unique_id FROM profiled_patients)) AS altered_patients,
    round((SELECT count() FROM altered_patients WHERE patient_unique_id IN (SELECT patient_unique_id FROM profiled_patients)) * 100.0 / (SELECT count() FROM profiled_patients), 1) AS frequency_pct
"
}

◀ result
{"error_message":"Query execution failed: HTTPDriver for https://dl96orhu96.us-east-1.aws.clickhouse.cloud:8443 received ClickHouse error code 47\n Code: 47. DB::Exception: Unknown expression or table expression identifier `patient_unique_id` in scope (SELECT count() FROM altered_patients WHERE patient_unique_id IN (SELECT patient_unique_id FROM profiled_patients)) AS altered_patients. (UNKNOWN_IDENTIFIER) (version 26.4.1.2359 (official build))\n"}

▶ clickhouse_run_select_query
{
 "query": "
WITH profiled_patients AS (
    SELECT DISTINCT c.patient_unique_id AS patient_unique_id
    FROM sample_to_gene_panel_derived s
    JOIN (SELECT DISTINCT sample_unique_id, patient_unique_id FROM clinical_data_derived
          WHERE cancer_study_identifier = 'msk_chord_2024') c USING (sample_unique_id)
    WHERE s.cancer_study_identifier = 'msk_chord_2024' AND s.alteration_type = 'MUTATION_EXTENDED'
),
altered_patients AS (
    SELECT DISTINCT c.patient_unique_id AS patient_unique_id
    FROM genomic_event_derived g
    JOIN (SELECT DISTINCT sample_unique_id, patient_unique_id FROM clinical_data_derived
          WHERE cancer_study_identifier = 'msk_chord_2024') c USING (sample_unique_id)
    WHERE g.cancer_study_identifier = 'msk_chord_2024'
      AND g.variant_type = 'mutation'
      AND g.mutation_status != 'UNCALLED'
      AND g.hugo_gene_symbol = 'TP53'
      AND g.off_panel = 0
)
SELECT
    (SELECT count() FROM profiled_patients) AS n_profiled,
    (SELECT count() FROM altered_patients a WHERE a.patient_unique_id IN (SELECT patient_unique_id FROM profiled_patients)) AS n_altered,
    round((SELECT count() FROM altered_patients a WHERE a.patient_unique_id IN (SELECT patient_unique_id FROM profiled_patients)) * 100.0 / (SELECT count() FROM profiled_patients), 1) AS frequency_pct
"
}

◀ result
{"rows":[{"n_profiled":24950,"n_altered":13105,"frequency_pct":52.5}]}

▶ resolve_and_route
{
 "studyIds": [
  "msk_chord_2024"
 ]
}

◀ result
{"success":true,"message":"Found 1 study. Use the metadata to call the appropriate navigation tool(s).","data":{"totalCount":1,"studiesWithMetadata":[{"studyId":"msk_chord_2024","name":"MSK-CHORD (MSK, Nature 2024)","sampleCount":25040,"studyViewUrl":"https://www.cbioportal.org/study?id=msk_chord_2024","metadata":{"clinicalAttributeIds":["ADRENAL_GLANDS","BONE","CANCER_TYPE","CANCER_TYPE_DETAILED","CLINICAL_GROUP","CLINICAL_SUMMARY","CNS_BRAIN","CURRENT_AGE_DEID","DIAGNOSIS_DESCRIPTION","ETHNICITY","FRACTION_GENOME_ALTERED","GENDER","GENE_PANEL","GLEASON_FIRST_REPORTED","GLEASON_HIGHEST_REPORTED","GLEASON_SAMPLE_LEVEL","HER2","HISTORY_OF_PDL1","HR","ICD_O_HISTOLOGY_DESCRIPTION","INTRA_ABDOMINAL","LIVER","LUNG","LYMPH_NODES","METASTATIC_SITE","MSI_COMMENT","MSI_SCORE","MSI_TYPE","MUTATION_COUNT","NUM_ICDO_DX","ONCOTREE_CODE","OS_MONTHS","OS_STATUS","OTHER","PATHOLOGICAL_GROUP","PDL1_POSITIVE","PLEURA","PRIMARY_SITE","PRIOR_MED_TO_MSK","RACE","REPRODUCTIVE_ORGANS","SAMPLE_CLASS","SAMPLE_COUNT","SAMPLE_COVERAGE","SAMPLE_TYPE","SMOKING_PREDICTIONS_3_CLASSES","SOMATIC_STATUS","STAGE_HIGHEST_RECORDED","TMB_NONSYNONYMOUS","TUMOR_PURITY"],"molecularProfileIds":["msk_chord_2024_cna","msk_chord_2024_mutations","msk_chord_2024_structural_variants"],"availableComparisonTabs":["overlap","clinical","survival","alterations","mutations"]}}]}}

▶ navigate_to_results_view
{
 "studyIds": [
  "msk_chord_2024"
 ],
 "genes": [
  "TP53: MUT"
 ],
 "tab": "mutations"
}

◀ result
{"success":true,"message":"Navigating to https://www.cbioportal.org/results/mutations?cancer_study_list=msk_chord_2024&gene_list=TP53%3A+MUT&case_set_id=msk_chord_2024_all","url":"https://www.cbioportal.org/results/mutations?cancer_study_list=msk_chord_2024&gene_list=TP53%3A+MUT&case_set_id=msk_chord_2024_all","data":{"studyIds":["msk_chord_2024"],"studies":[{"studyId":"msk_chord_2024","name":"MSK-CHORD (MSK, Nature 2024)","sampleCount":25040}],"genes":["TP53"],"caseSetId":"msk_chord_2024_all","pageDescription":"Detailed mutation table with lollipop plot showing mutation positions, types, and frequencies for queried genes."}}

▶ navigate_to_study_view
{
 "studyIds": [
  "msk_chord_2024"
 ],
 "filterJson": {
  "geneFilters": [
   {
    "molecularProfileIds": [
     "msk_chord_2024_mutations"
    ],
    "geneQueries": [
     [
      {
       "hugoGeneSymbol": "TP53"
      }
     ]
    ]
   }
  ]
 }
}

◀ result
{"success":true,"message":"Navigating to https://www.cbioportal.org/study/summary?id=msk_chord_2024#filterJson=%7B%22geneFilters%22%3A%5B%7B%22geneQueries%22%3A%5B%5B%7B%22hugoGeneSymbol%22%3A%22TP53%22%7D%5D%5D%2C%22molecularProfileIds%22%3A%5B%22msk_chord_2024_mutations%22%5D%7D%5D%7D","url":"https://www.cbioportal.org/study/summary?id=msk_chord_2024#filterJson=%7B%22geneFilters%22%3A%5B%7B%22geneQueries%22%3A%5B%5B%7B%22hugoGeneSymbol%22%3A%22TP53%22%7D%5D%5D%2C%22molecularProfileIds%22%3A%5B%22msk_chord_2024_mutations%22%5D%7D%5D%7D","data":{"studyIds":["msk_chord_2024"],"studies":[{"studyId":"msk_chord_2024","name":"MSK-CHORD (MSK, Nature 2024)","sampleCount":25040}],"tab":"summary","hasFilters":true,"hasPlotsConfig":false,"pageDescription":"Overview of all study data displayed as interactive charts summarizing available clinical and genomic data. Click within a chart to filter. Additional charts may be available in the Charts menu."}}

═ answer (success)
## TP53 mutation prevalence in MSK-CHORD

In the **MSK-CHORD** study (MSK, *Nature* 2024; 25,040 samples across colorectal, non-small cell lung, breast, prostate, and pancreatic cancer), **13,105 of 24,950 patients profiled for mutations (52.5%)** carry at least one TP53 mutation (patient-level, on-panel calls only, excluding uncalled variants).

TP53 mutation frequency varies considerably by cancer type in this cohort (sample-level):

| Cancer Type | Altered / Profiled | Frequency |
|---|---|---|
| Colorectal Cancer | 4,068 / 5,543 | 73.4% |
| Pancreatic Cancer | 2,076 / 3,109 | 66.8% |
| Non-Small Cell Lung Cancer | 4,005 / 7,809 | 51.3% |
| Breast Cancer | 2,138 / 5,368 | 39.8% |
| Prostate Cancer | 837 / 3,211 | 26.1% |

The overall 52.5% figure is a pooled average across these five cancer types with very different baseline TP53 rates — the per-cancer-type numbers above are more informative for any single tumor type.

**Explore further:**
- [TP53 mutation details (lollipop plot, variant table)](https://www.cbioportal.org/results/mutations?cancer_study_list=msk_chord_2024&gene_list=TP53%3A+MUT&case_set_id=msk_chord_2024_all)
- [Study cohort filtered to TP53-mutant samples](https://www.cbioportal.org/study/summary?id=msk_chord_2024#filterJson=%7B%22geneFilters%22%3A%5B%7B%22geneQueries%22%3A%5B%5B%7B%22hugoGeneSymbol%22%3A%22TP53%22%7D%5D%5D%2C%22molecularProfileIds%22%3A%5B%22msk_chord_2024_mutations%22%5D%7D%5D%7D)