Q (haiku): What are the EGFR mutation frequencies across cancer types in the MSK-IMPACT 50K study? ▶ read_guide { "uri": "cbioportal://mutation-frequency-guide" } ▶ list_studies { "search": "MSK-IMPACT 50K", "verbose": true } ◀ 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 {"result":[{"cancer_study_identifier":"msk_impact_50k_2026","name":"MSK-IMPACT 50K Clinical Sequencing Cohort (MSK, Cancer Cell 2026)","description":"MSK-50K (Memorial Sloan Kettering - 50,000 patients) is a pan-cancer clinical sequencing cohort of 54,331 tumors and their matched normal samples, profiled using MSK-IMPACT. The dataset includes somatic mutations, gene-level copy number alterations, structural variants in select genes, genome-wide allele-specific copy number, cancer cell fractions of mutations, derived mutational signatures, whole genome doubling status, and somatic/germline HLA Class I Genotype data. This data is available under the Creative Commons BY-NC-ND 4.0 license. For commercial use, please contact datarequests@mskcc.org.","type_of_cancer_id":"mixed","sample_count":54331,"has_guide":false,"url":"https://www.cbioportal.org/study/summary?id=msk_impact_50k_2026"}]} ▶ clickhouse_run_select_query { "query": " SELECT * FROM gene_mutation_frequency_in_study( study = 'msk_impact_50k_2026', gene = 'EGFR' ) ORDER BY frequency_pct DESC ", "max_rows": 100 } ◀ result {"rows":[{"cancer_type":"Non-Small Cell Lung Cancer","altered_samples":2060,"profiled_samples":7867,"frequency_pct":26.2},{"cancer_type":"Glioma","altered_samples":353,"profiled_samples":2322,"frequency_pct":15.2},{"cancer_type":"Small Cell Lung Cancer","altered_samples":42,"profiled_samples":466,"frequency_pct":9},{"cancer_type":"Melanoma","altered_samples":131,"profiled_samples":1831,"frequency_pct":7.2},{"cancer_type":"Skin Cancer, Non-Melanoma","altered_samples":26,"profiled_samples":455,"frequency_pct":5.7},{"cancer_type":"Miscellaneous Brain Tumor","altered_samples":3,"profiled_samples":58,"frequency_pct":5.2},{"cancer_type":"Endometrial Cancer","altered_samples":105,"profiled_samples":2445,"frequency_pct":4.3},{"altered_samples":2,"profiled_samples":50,"frequency_pct":4},{"cancer_type":"Bladder Cancer","altered_samples":87,"profiled_samples":2526,"frequency_pct":3.4},{"cancer_type":"Cancer of Unknown Primary","altered_samples":41,"profiled_samples":1581,"frequency_pct":2.6},{"cancer_type":"Colorectal Cancer","altered_samples":135,"profiled_samples":5277,"frequency_pct":2.6},{"cancer_type":"Small Bowel Cancer","altered_samples":4,"profiled_samples":161,"frequency_pct":2.5},{"cancer_type":"Adrenocortical Carcinoma","altered_samples":2,"profiled_samples":88,"frequency_pct":2.3},{"cancer_type":"Anal Cancer","altered_samples":3,"profiled_samples":143,"frequency_pct":2.1},{"cancer_type":"Esophagogastric Cancer","altered_samples":38,"profiled_samples":1834,"frequency_pct":2.1},{"cancer_type":"Head and Neck Cancer","altered_samples":12,"profiled_samples":657,"frequency_pct":1.8},{"cancer_type":"Breast Cancer","altered_samples":100,"profiled_samples":6807,"frequency_pct":1.5},{"cancer_type":"Uterine Sarcoma","altered_samples":5,"profiled_samples":344,"frequency_pct":1.5},{"cancer_type":"Ampullary Cancer","altered_samples":2,"profiled_samples":134,"frequency_pct":1.5},{"cancer_type":"Hepatobiliary Cancer","altered_samples":17,"profiled_samples":1431,"frequency_pct":1.2},{"cancer_type":"Salivary Gland Cancer","altered_samples":4,"profiled_samples":411,"frequency_pct":1},{"cancer_type":"Cervical Cancer","altered_samples":3,"profiled_samples":351,"frequency_pct":0.9},{"cancer_type":"Prostate Cancer","altered_samples":30,"profiled_samples":3324,"frequency_pct":0.9},{"cancer_type":"Sellar Tumor","altered_samples":1,"profiled_samples":106,"frequency_pct":0.9},{"cancer_type":"Germ Cell Tumor","altered_samples":6,"profiled_samples":725,"frequency_pct":0.8},{"cancer_type":"Ovarian Cancer","altered_samples":18,"profiled_samples":2140,"frequency_pct":0.8},{"cancer_type":"Appendiceal Cancer","altered_samples":2,"profiled_samples":274,"frequency_pct":0.7},{"cancer_type":"Thyroid Cancer","altered_samples":6,"profiled_samples":867,"frequency_pct":0.7},{"cancer_type":"Pancreatic Cancer","altered_samples":16,"profiled_samples":2851,"frequency_pct":0.6},{"cancer_type":"Renal Cell Carcinoma","altered_samples":7,"profiled_samples":1209,"frequency_pct":0.6},{"cancer_typ … (404 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": [ "EGFR" ], "tab": "oncoprint" } ◀ result {"success":true,"message":"Navigating to https://www.cbioportal.org/results/oncoprint?cancer_study_list=msk_impact_50k_2026&gene_list=EGFR&case_set_id=msk_impact_50k_2026_all","url":"https://www.cbioportal.org/results/oncoprint?cancer_study_list=msk_impact_50k_2026&gene_list=EGFR&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":["EGFR"],"caseSetId":"msk_impact_50k_2026_all","pageDescription":"Visual summary of alterations in queried genes across samples."}} ═ answer (success) ## EGFR Mutation Frequencies Across Cancer Types in MSK-IMPACT 50K Based on the MSK-IMPACT 50K Clinical Sequencing Cohort (**54,331 tumors**), here are **EGFR mutation frequencies by cancer type** (sample-level): ### Top Cancer Types with EGFR Mutations | Cancer Type | EGFR Mutations | Profiled Samples | Frequency | |---|---:|---:|---:| | **Non-Small Cell Lung Cancer** | 2,060 | 7,867 | **26.2%** | | **Glioma** | 353 | 2,322 | **15.2%** | | **Small Cell Lung Cancer** | 42 | 466 | **9.0%** | | **Melanoma** | 131 | 1,831 | **7.2%** | | **Skin Cancer, Non-Melanoma** | 26 | 455 | **5.7%** | | **Miscellaneous Brain Tumor** | 3 | 58 | **5.2%** | | **Endometrial Cancer** | 105 | 2,445 | **4.3%** | | **Bladder Cancer** | 87 | 2,526 | **3.4%** | | **Colorectal Cancer** | 135 | 5,277 | **2.6%** | ### Key Insights - **EGFR dominates in lung cancer:** Nearly 1 in 4 non-small cell lung cancers carry EGFR mutations (26.2%), making this the primary driver alteration in that disease. - **Significant enrichment in CNS tumors:** Glioma (15.2%) and brain tumors (5.2%) show substantial EGFR mutation rates, consistent with EGFR's role in glial malignancies. - **Lower frequencies in epithelial tumors:** Breast (1.5%), prostate (0.9%), and ovarian cancers (0.8%) have minimal EGFR mutation rates, reflecting their distinct genomic landscapes. ### Explore Further [View EGFR alterations across all cancer types in OncoPrint](https://www.cbioportal.org/results/oncoprint?cancer_study_list=msk_impact_50k_2026&gene_list=EGFR&case_set_id=msk_impact_50k_2026_all) — includes mutations, copy number alterations, and structural variants.