Q (haiku): What is the frequency of TP53 mutations in lung cancer? ▶ read_guide { "uri": "cbioportal://mutation-frequency-guide" } ▶ search_oncotree { "search_term": "lung cancer" } ◀ 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":[{"code":"LUNG","name":"Lung","score":65,"mainType":"Lung Cancer","tissue":"Lung","hierarchy":"LUNG"},{"code":"NSCLC","name":"Non-Small Cell Lung Cancer","score":50,"mainType":"Non-Small Cell Lung Cancer","tissue":"Lung","hierarchy":"LUNG > NSCLC"},{"code":"NSCLCPD","name":"Poorly Differentiated Non-Small Cell Lung Cancer","score":50,"mainType":"Non-Small Cell Lung Cancer","tissue":"Lung","hierarchy":"LUNG > NSCLC > NSCLCPD"},{"code":"SCLC","name":"Small Cell Lung Cancer","score":50,"mainType":"Small Cell Lung Cancer","tissue":"Lung","hierarchy":"LUNG > LNET > SCLC"},{"code":"ALUCA","name":"Atypical Lung Carcinoid","score":45,"mainType":"Non-Small Cell Lung Cancer","tissue":"Lung","hierarchy":"LUNG > LNET > ALUCA"},{"code":"BLCLC","name":"Basaloid Large Cell Carcinoma of the Lung","score":45,"mainType":"Non-Small Cell Lung Cancer","tissue":"Lung","hierarchy":"LUNG > NSCLC > LCLC > BLCLC"},{"code":"CCLC","name":"Clear Cell Carcinoma of the Lung","score":45,"mainType":"Non-Small Cell Lung Cancer","tissue":"Lung","hierarchy":"LUNG > NSCLC > LCLC > CCLC"},{"code":"CMPT","name":"Ciliated Muconodular Papillary Tumor of the Lung","score":45,"mainType":"Non-Small Cell Lung Cancer","tissue":"Lung","hierarchy":"LUNG > NSCLC > CMPT"},{"code":"CSCLC","name":"Combined Small Cell Lung Carcinoma","score":45,"mainType":"Small Cell Lung Cancer","tissue":"Lung","hierarchy":"LUNG > CSCLC"},{"code":"GCLC","name":"Giant Cell Carcinoma of the Lung","score":45,"mainType":"Non-Small Cell Lung Cancer","tissue":"Lung","hierarchy":"LUNG > NSCLC > LCLC > GCLC"},{"code":"IMTL","name":"Inflammatory Myofibroblastic Lung Tumor","score":45,"mainType":"Non-Small Cell Lung Cancer","tissue":"Lung","hierarchy":"LUNG > IMTL"},{"code":"LAIS","name":"Lung Adenocarcinoma In Situ","score":45,"mainType":"Non-Small Cell Lung Cancer","tissue":"Lung","hierarchy":"LUNG > LAIS"},{"code":"LAM","name":"Pulmonary Lymphangiomyomatosis","score":45,"mainType":"Non-Small Cell Lung Cancer","tissue":"Lung","hierarchy":"LUNG > LAM"},{"code":"LCLC","name":"Large Cell Lung Carcinoma","score":45,"mainType":"Non-Small Cell Lung Cancer","tissue":"Lung","hierarchy":"LUNG > NSCLC > LCLC"},{"code":"LECLC","name":"Lymphoepithelioma-like Carcinoma of the Lung","score":45,"mainType":"Non-Small Cell Lung Cancer","tissue":"Lung","hierarchy":"LUNG > NSCLC > LCLC > LECLC"},{"code":"LNET","name":"Lung Neuroendocrine Tumor","score":45,"mainType":"Non-Small Cell Lung Cancer","tissue":"Lung","hierarchy":"LUNG > LNET"},{"code":"LUACC","name":"Adenoid Cystic Carcinoma of the Lung","score":45,"mainType":"Non-Small Cell Lung Cancer","tissue":"Lung","hierarchy":"LUNG > NSCLC > SGTTL > LUACC"},{"code":"LUAD","name":"Lung Adenocarcinoma","score":45,"mainType":"Non-Small Cell Lung Cancer","tissue":"Lung","hierarchy":"LUNG > NSCLC > LUAD"},{"code":"LUAS","name":"Lung Adenosquamous Carcinoma","score":45,"mainType":"Non-Small Cell Lung Cancer","tissue":"Lung","hierarchy":"LUNG > NSCLC > LUAS"},{"code":"LUCA","name":"Lung C … (915 more chars) ▶ clickhouse_run_select_query { "query": " SELECT * FROM gene_mutation_frequency_by_cancer_type( preference = 'pan_cancer_tcga', gene = 'TP53' ) WHERE cancer_type LIKE '%Lung%' OR cancer_type LIKE '%NSCLC%' OR cancer_type LIKE '%LUAD%' OR cancer_type LIKE '%LUSC%' ORDER BY frequency_pct DESC; ", "max_rows": 100 } ◀ result {"rows":[{"cancer_type":"Non-Small Cell Lung Cancer","altered_samples":699,"profiled_samples":1050,"frequency_pct":66.6}]} ▶ clickhouse_run_select_query { "query": " SELECT * FROM gene_mutation_frequency_in_studies( studies = ['luad_tcga_pan_can_atlas_2018', 'lusc_tcga_pan_can_atlas_2018'], gene = 'TP53' ) ORDER BY frequency_pct DESC; ", "max_rows": 100 } ◀ result {"rows":[{"cancer_type":"Non-Small Cell Lung Cancer","altered_samples":699,"profiled_samples":1050,"frequency_pct":66.6}]} ▶ clickhouse_run_select_query { "query": " SELECT * FROM gene_mutation_frequency_in_study( study = 'luad_tcga_pan_can_atlas_2018', gene = 'TP53' ); ", "max_rows": 100 } ▶ clickhouse_run_select_query { "query": " SELECT * FROM gene_mutation_frequency_in_study( study = 'lusc_tcga_pan_can_atlas_2018', gene = 'TP53' ); ", "max_rows": 100 } ◀ result {"rows":[{"cancer_type":"Non-Small Cell Lung Cancer","altered_samples":295,"profiled_samples":566,"frequency_pct":52.1}]} ◀ result {"rows":[{"cancer_type":"Non-Small Cell Lung Cancer","altered_samples":404,"profiled_samples":484,"frequency_pct":83.5}]} ▶ resolve_and_route { "studyIds": [ "luad_tcga_pan_can_atlas_2018", "lusc_tcga_pan_can_atlas_2018" ] } ◀ result {"success":true,"message":"Found 2 matching studies. 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":2,"studiesWithMetadata":[{"studyId":"luad_tcga_pan_can_atlas_2018","name":"Lung Adenocarcinoma (TCGA, PanCancer Atlas)","sampleCount":566,"studyViewUrl":"https://www.cbioportal.org/study?id=luad_tcga_pan_can_atlas_2018","metadata":{"clinicalAttributeIds":["AGE","AJCC_PATHOLOGIC_TUMOR_STAGE","AJCC_STAGING_EDITION","ANEUPLOIDY_SCORE","BUFFA_HYPOXIA_SCORE","CANCER_TYPE","CANCER_TYPE_ACRONYM","CANCER_TYPE_DETAILED","DAYS_LAST_FOLLOWUP","DAYS_TO_BIRTH","DAYS_TO_INITIAL_PATHOLOGIC_DIAGNOSIS","DFS_MONTHS","DFS_STATUS","DSS_MONTHS","DSS_STATUS","ETHNICITY","FORM_COMPLETION_DATE","FRACTION_GENOME_ALTERED","GENETIC_ANCESTRY_LABEL","GRADE","HISTORY_NEOADJUVANT_TRTYN","ICD_10","ICD_O_3_HISTOLOGY","ICD_O_3_SITE","INFORMED_CONSENT_VERIFIED","IN_PANCANPATHWAYS_FREEZE","MSI_SCORE_MANTIS","MSI_SENSOR_SCORE","MUTATION_COUNT","NEW_TUMOR_EVENT_AFTER_INITIAL_TREATMENT","ONCOTREE_CODE","OS_MONTHS","OS_STATUS","OTHER_PATIENT_ID","PATH_M_STAGE","PATH_N_STAGE","PATH_T_STAGE","PERSON_NEOPLASM_CANCER_STATUS","PFS_MONTHS","PFS_STATUS","PRIMARY_LYMPH_NODE_PRESENTATION_ASSESSMENT","PRIOR_DX","RACE","RADIATION_THERAPY","RAGNUM_HYPOXIA_SCORE","SAMPLE_COUNT","SAMPLE_TYPE","SEX","SOMATIC_STATUS","SUBTYPE","TBL_SCORE","TISSUE_PROSPECTIVE_COLLECTION_INDICATOR","TISSUE_RETROSPECTIVE_COLLECTION_INDICATOR","TISSUE_SOURCE_SITE","TISSUE_SOURCE_SITE_CODE","TMB_NONSYNONYMOUS","TUMOR_TISSUE_SITE","TUMOR_TYPE","WEIGHT","WINTER_HYPOXIA_SCORE"],"molecularProfileIds":["luad_tcga_pan_can_atlas_2018_gistic","luad_tcga_pan_can_atlas_2018_log2CNA","luad_tcga_pan_can_atlas_2018_mutations","luad_tcga_pan_can_atlas_2018_rna_seq_v2_mrna","luad_tcga_pan_can_atlas_2018_rna_seq_v2_mrna_median_Zscores","luad_tcga_pan_can_atlas_2018_rna_seq_v2_mrna_median_all_sample_Zscores","luad_tcga_pan_can_atlas_2018_rna_seq_v2_mrna_median_all_sample_ref_normal_Zscores","luad_tcga_pan_can_atlas_2018_rppa","luad_tcga_pan_can_atlas_2018_rppa_Zscores","luad_tcga_pan_can_atlas_2018_structural_variants"],"genericAssayProfiles":["luad_tcga_pan_can_atlas_2018_armlevel_cna","luad_tcga_pan_can_atlas_2018_genetic_ancestry","luad_tcga_pan_can_atlas_2018_methylation_hm27_hm450_merge","luad_tcga_pan_can_atlas_2018_methylation_hm450"],"heatmapProfileIds":["luad_tcga_pan_can_atlas_2018_rna_seq_v2_mrna_median_Zscores","luad_tcga_pan_can_atlas_2018_rna_seq_v2_mrna_median_all_sample_Zscores","luad_tcga_pan_can_atlas_2018_rna_seq_v2_mrna_median_all_sample_ref_normal_Zscores","luad_tcga_pan_can_atlas_2018_rppa_Zscores"],"availableComparisonTabs":["overlap","clinical","survival","alterations","mutations","mrna","protein","generic_assay_armlevel_cna","generic_assay_genetic_ancestry","generic_assay_methylation"]}},{"studyId":"lusc_tcga_pan_can_atlas_2018","name":"Lung Squamous Cell … (2585 more chars) ▶ navigate_to_results_view { "studyIds": [ "luad_tcga_pan_can_atlas_2018", "lusc_tcga_pan_can_atlas_2018" ], "genes": [ "TP53" ], "tab": "oncoprint" } ◀ result {"success":true,"message":"Navigating to https://www.cbioportal.org/results/oncoprint?cancer_study_list=luad_tcga_pan_can_atlas_2018%2Clusc_tcga_pan_can_atlas_2018&gene_list=TP53&case_set_id=all","url":"https://www.cbioportal.org/results/oncoprint?cancer_study_list=luad_tcga_pan_can_atlas_2018%2Clusc_tcga_pan_can_atlas_2018&gene_list=TP53&case_set_id=all","data":{"studyIds":["luad_tcga_pan_can_atlas_2018","lusc_tcga_pan_can_atlas_2018"],"studies":[{"studyId":"luad_tcga_pan_can_atlas_2018","name":"Lung Adenocarcinoma (TCGA, PanCancer Atlas)","sampleCount":566},{"studyId":"lusc_tcga_pan_can_atlas_2018","name":"Lung Squamous Cell Carcinoma (TCGA, PanCancer Atlas)","sampleCount":487}],"genes":["TP53"],"caseSetId":"all","pageDescription":"Visual summary of alterations in queried genes across samples."}} ═ answer (success) ## TP53 Mutation Frequency in Lung Cancer **Counting unit:** Sample-level frequency (altered samples / profiled samples). ### Overall Lung Cancer (Pooled) **TP53 is mutated in 66.6%** (699/1,050 samples) across TCGA lung cancer studies. ### By Histological Subtype | Subtype | TP53 Mutations | Frequency | |---------|---|---| | **Lung Adenocarcinoma (LUAD)** | 295/566 | **52.1%** | | **Lung Squamous Cell Carcinoma (LUSC)** | 404/484 | **83.5%** | The higher frequency in squamous cell carcinoma reflects the distinct mutational landscapes of the two subtypes — TP53 is a major driver in LUSC, whereas adenocarcinoma carries a broader spectrum of driver mutations (e.g., EGFR, KRAS, ALK). ### Explore the Data [View TP53 mutations across TCGA lung adenocarcinoma and squamous cell carcinoma](https://www.cbioportal.org/results/oncoprint?cancer_study_list=luad_tcga_pan_can_atlas_2018%2Clusc_tcga_pan_can_atlas_2018&gene_list=TP53&case_set_id=all) This OncoPrint visualization shows the distribution and types of TP53 alterations (mutations, CNAs) across both cohorts.