Q (haiku): What is the frequency of TP53 mutations in lung cancer?

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

▶ resolve_and_route
{
 "studyKeywords": [
  "lung"
 ]
}

◀ 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)

◀ result
{"success":true,"message":"Found 43 matching studies (top 5 with full metadata, rest with basic info). Pick the best match (prefer TCGA → prefer PanCancer Atlas), use its metadata to call the appropriate navigation tool(s) and generate URLs immediately. Present other studies as alternatives.","data":{"totalCount":43,"studiesWithMetadata":[{"studyId":"msk_met_2021","name":"MSK MetTropism (MSK, Cell 2021)","sampleCount":25775,"studyViewUrl":"https://www.cbioportal.org/study?id=msk_met_2021","metadata":{"clinicalAttributeIds":["AGE_AT_DEATH","AGE_AT_EVIDENCE_OF_METS","AGE_AT_LAST_CONTACT","AGE_AT_SEQUENCING","AGE_AT_SURGERY","CANCER_TYPE","CANCER_TYPE_DETAILED","DMETS_DX_ADRENAL_GLAND","DMETS_DX_BILIARY_TRACT","DMETS_DX_BLADDER_UT","DMETS_DX_BONE","DMETS_DX_BOWEL","DMETS_DX_BREAST","DMETS_DX_CNS_BRAIN","DMETS_DX_DIST_LN","DMETS_DX_FEMALE_GENITAL","DMETS_DX_HEAD_NECK","DMETS_DX_INTRA_ABDOMINAL","DMETS_DX_KIDNEY","DMETS_DX_LIVER","DMETS_DX_LUNG","DMETS_DX_MALE_GENITAL","DMETS_DX_MEDIASTINUM","DMETS_DX_OVARY","DMETS_DX_PLEURA","DMETS_DX_PNS","DMETS_DX_SKIN","DMETS_DX_UNSPECIFIED","FGA","FRACTION_GENOME_ALTERED","GENE_PANEL","IS_DIST_MET_MAPPED","METASTATIC_SITE","MET_COUNT","MET_SITE_COUNT","MSI_SCORE","MSI_TYPE","MUTATION_COUNT","ONCOTREE_CODE","ORGAN_SYSTEM","OS_MONTHS","OS_STATUS","PRIMARY_SITE","RACE","SAMPLE_COUNT","SAMPLE_COVERAGE","SAMPLE_TYPE","SEX","SUBTYPE","SUBTYPE_ABBREVIATION","TMB_NONSYNONYMOUS","TUMOR_PURITY"],"molecularProfileIds":["msk_met_2021_cna","msk_met_2021_mutations","msk_met_2021_structural_variants"],"availableComparisonTabs":["overlap","clinical","survival","alterations","mutations"]}},{"studyId":"luad_mskcc_2023_met_organotropism","name":"Lung Adenocarcinoma Met Organotropism (MSK, Cancer Cell 2023)","sampleCount":2653,"studyViewUrl":"https://www.cbioportal.org/study?id=luad_mskcc_2023_met_organotropism","metadata":{"clinicalAttributeIds":["ADJUVANT","ADJUVANT_CHEMOTHERAPY","ADJUVANT_IMMUNOTHERAPY","ADJUVANT_TARGETED","ADJUVANT_THERAPY","ADJUVANT_XRT","ADRENAL_MONTHS","ADRENAL_STATUS","AGE_AT_DOS_BX","BONE_MONTHS","BONE_STATUS","CANCER_TYPE","CANCER_TYPE_DETAILED","CELL_CYCLE","CIGARETTE_HX","CNS_MONTHS","CNS_STATUS","CSTAGE","DEATH","EVER_MET_SITE_ADRENAL","EVER_MET_SITE_BONE","EVER_MET_SITE_CNS","EVER_MET_SITE_LIVER_BILIARY_TRACT","EVER_MET_SITE_LN","EVER_MET_SITE_LUNG","EVER_MET_SITE_PLEURA","FGA","FRACTION_GENOME_ALTERED","FU_2YRS","GENE_PANEL","GROUP_NO","HAD_SURGERY","HIPPO","IMPACT_METASTATIC_LESION","IMPACT_PRIMARY_GROUP","INSTITUTE","IN_MATCHED","IS_WGD","LIVER_MONTHS","LIVER_STATUS","LN_MONTHS","LN_STATUS","LUNG_MONTHS","LUNG_STATUS","METASTATIC_BURDEN","METASTATIC_SITE","MONTHS_FROM_MATCHED_PRIM","MSI_SCORE","MSI_TYPE","MUTATION_COUNT","MYC_PATH","NEOADJUVANT","NEOADJUVANT_CHEMOTHERAPY","NEOADJUVANT_IMMUNOTHERAPY","NEOADJUVANT_TARGETED","NEOADJUVANT_XRT","NOTCH","NRF2","ONCOTREE_CODE","OS_MONTHS","OS_STATUS","PI3K","PLEURA_MONTHS","PLEURA_STATUS","PLOIDY","POST_SAMPLE_CHEMOTHERAPY","POST_SAMPLE_IMMUNOTHERAPY","POS … (12605 more chars)

▶ clickhouse_run_select_query
{
 "query": "
SELECT *
FROM gene_mutation_frequency_in_study(
    study = 'luad_tcga_pan_can_atlas_2018',
    gene  = 'TP53'
)
"
}

◀ result
{"rows":[{"cancer_type":"Non-Small Cell Lung Cancer","altered_samples":295,"profiled_samples":566,"frequency_pct":52.1}]}

▶ navigate_to_results_view
{
 "studyIds": [
  "luad_tcga_pan_can_atlas_2018"
 ],
 "genes": [
  "TP53"
 ],
 "tab": "mutations"
}

◀ result
{"success":true,"message":"Navigating to https://www.cbioportal.org/results/mutations?cancer_study_list=luad_tcga_pan_can_atlas_2018&gene_list=TP53&case_set_id=luad_tcga_pan_can_atlas_2018_all","url":"https://www.cbioportal.org/results/mutations?cancer_study_list=luad_tcga_pan_can_atlas_2018&gene_list=TP53&case_set_id=luad_tcga_pan_can_atlas_2018_all","data":{"studyIds":["luad_tcga_pan_can_atlas_2018"],"studies":[{"studyId":"luad_tcga_pan_can_atlas_2018","name":"Lung Adenocarcinoma (TCGA, PanCancer Atlas)","sampleCount":566}],"genes":["TP53"],"caseSetId":"luad_tcga_pan_can_atlas_2018_all","pageDescription":"Detailed mutation table with lollipop plot showing mutation positions, types, and frequencies for queried genes."}}

═ answer (success)
## TP53 Mutation Frequency in Lung Cancer

**TP53 is mutated in 52.1% of lung adenocarcinomas.**

Based on the **TCGA PanCancer Atlas**, a canonical reference dataset of 566 lung adenocarcinoma samples:

| Gene | Mutated Samples | Profiled Samples | Frequency |
|------|-----------------|------------------|-----------|
| **TP53** | 295 | 566 | **52.1%** |

This represents a **sample-level frequency**. TP53 is one of the most frequently mutated genes in lung adenocarcinoma and is considered a classic tumor suppressor in this cancer type.

### Explore the Data

[View TP53 mutations in lung adenocarcinoma](https://www.cbioportal.org/results/mutations?cancer_study_list=luad_tcga_pan_can_atlas_2018&gene_list=TP53&case_set_id=luad_tcga_pan_can_atlas_2018_all) — This link shows a detailed mutation table with the most common TP53 variants (mutation types, protein changes, and frequencies) and a lollipop plot mapping mutations across the TP53 protein structure.

---

### Additional Lung Cancer Studies

If you want to compare across different lung cohorts or cancer subtypes (e.g., squamous cell carcinoma, small-cell lung cancer), here are other lung cancer studies available:
- **TCGA Lung Squamous Cell Carcinoma** (487 samples) — TP53 has a higher mutation rate in squamous carcinoma
- **MSK Non-Small Cell Lung Cancer** (915 samples) — comprehensive targeted genomics
- **MSK Metastatic Lung Adenocarcinoma** (2,653 samples) — includes metastatic disease

Would you like me to check TP53 mutation frequency in other lung cancer studies or subtypes?