Q (haiku): compare egfr mutations between lung and brain cancer

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

▶ search_oncotree
{
 "search_term": "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 … (35166 more chars)

▶ search_oncotree
{
 "search_term": "brain"
}

◀ result
{"result":[{"code":"LUNG","name":"Lung","score":100,"mainType":"Lung Cancer","tissue":"Lung","hierarchy":"LUNG"},{"code":"LAIS","name":"Lung Adenocarcinoma In Situ","score":60,"mainType":"Non-Small Cell Lung Cancer","tissue":"Lung","hierarchy":"LUNG > LAIS"},{"code":"LNET","name":"Lung Neuroendocrine Tumor","score":60,"mainType":"Non-Small Cell Lung Cancer","tissue":"Lung","hierarchy":"LUNG > LNET"},{"code":"LUAD","name":"Lung Adenocarcinoma","score":60,"mainType":"Non-Small Cell Lung Cancer","tissue":"Lung","hierarchy":"LUNG > NSCLC > LUAD"},{"code":"LUAS","name":"Lung Adenosquamous Carcinoma","score":60,"mainType":"Non-Small Cell Lung Cancer","tissue":"Lung","hierarchy":"LUNG > NSCLC > LUAS"},{"code":"LUCA","name":"Lung Carcinoid","score":60,"mainType":"Non-Small Cell Lung Cancer","tissue":"Lung","hierarchy":"LUNG > LNET > LUCA"},{"code":"LUSC","name":"Lung Squamous Cell Carcinoma","score":60,"mainType":"Non-Small Cell Lung Cancer","tissue":"Lung","hierarchy":"LUNG > NSCLC > LUSC"},{"code":"ALUCA","name":"Atypical Lung Carcinoid","score":50,"mainType":"Non-Small Cell Lung Cancer","tissue":"Lung","hierarchy":"LUNG > LNET > ALUCA"},{"code":"BLCLC","name":"Basaloid Large Cell Carcinoma of the Lung","score":50,"mainType":"Non-Small Cell Lung Cancer","tissue":"Lung","hierarchy":"LUNG > NSCLC > LCLC > BLCLC"},{"code":"CCLC","name":"Clear Cell Carcinoma of the Lung","score":50,"mainType":"Non-Small Cell Lung Cancer","tissue":"Lung","hierarchy":"LUNG > NSCLC > LCLC > CCLC"},{"code":"CMPT","name":"Ciliated Muconodular Papillary Tumor of the Lung","score":50,"mainType":"Non-Small Cell Lung Cancer","tissue":"Lung","hierarchy":"LUNG > NSCLC > CMPT"},{"code":"CSCLC","name":"Combined Small Cell Lung Carcinoma","score":50,"mainType":"Small Cell Lung Cancer","tissue":"Lung","hierarchy":"LUNG > CSCLC"},{"code":"GCLC","name":"Giant Cell Carcinoma of the Lung","score":50,"mainType":"Non-Small Cell Lung Cancer","tissue":"Lung","hierarchy":"LUNG > NSCLC > LCLC > GCLC"},{"code":"IMTL","name":"Inflammatory Myofibroblastic Lung Tumor","score":50,"mainType":"Non-Small Cell Lung Cancer","tissue":"Lung","hierarchy":"LUNG > IMTL"},{"code":"LCLC","name":"Large Cell Lung Carcinoma","score":50,"mainType":"Non-Small Cell Lung Cancer","tissue":"Lung","hierarchy":"LUNG > NSCLC > LCLC"},{"code":"LECLC","name":"Lymphoepithelioma-like Carcinoma of the Lung","score":50,"mainType":"Non-Small Cell Lung Cancer","tissue":"Lung","hierarchy":"LUNG > NSCLC > LCLC > LECLC"},{"code":"LUACC","name":"Adenoid Cystic Carcinoma of the Lung","score":50,"mainType":"Non-Small Cell Lung Cancer","tissue":"Lung","hierarchy":"LUNG > NSCLC > SGTTL > LUACC"},{"code":"LUMEC","name":"Mucoepidermoid Carcinoma of the Lung","score":50,"mainType":"Non-Small Cell Lung Cancer","tissue":"Lung","hierarchy":"LUNG > NSCLC > SGTTL > LUMEC"},{"code":"LUPC","name":"Pleomorphic Carcinoma of the Lung","score":50,"mainType":"Non-Small Cell Lung Cancer","tissue":"Lung","hierarchy":"LUNG > NSCLC > LUPC"},{"code":"NSCLC","na … (947 more chars)

◀ result
{"result":[{"code":"BRAIN","name":"CNS/Brain","score":100,"mainType":"CNS/Brain Cancer","tissue":"CNS/Brain","hierarchy":"BRAIN"},{"code":"BGCT","name":"Germ Cell Tumor, Brain","score":50,"mainType":"Germ Cell Tumor","tissue":"CNS/Brain","hierarchy":"BRAIN > BGCT"},{"code":"MBT","name":"Miscellaneous Brain Tumor","score":50,"mainType":"Miscellaneous Brain Tumor","tissue":"CNS/Brain","hierarchy":"BRAIN > MBT"},{"code":"PBT","name":"Primary Brain Tumor","score":50,"mainType":"Miscellaneous Brain Tumor","tissue":"CNS/Brain","hierarchy":"BRAIN > MBT > PBT"},{"code":"HGNET","name":"High-Grade Neuroepithelial Tumor","score":45,"mainType":"Miscellaneous Brain Tumor","tissue":"CNS/Brain","hierarchy":"BRAIN > MBT > HGNET"},{"code":"HMBL","name":"Hemangioblastoma","score":45,"mainType":"Miscellaneous Brain Tumor","tissue":"CNS/Brain","hierarchy":"BRAIN > MBT > HMBL"},{"code":"LGNET","name":"Polymorphous Low-Grade Neuroepithelial Tumor of the Young","score":45,"mainType":"Miscellaneous Brain Tumor","tissue":"CNS/Brain","hierarchy":"BRAIN > DIFG > PDIFLG > LGNET"},{"code":"MCHSCNS","name":"Mesenchymal Chondrosarcoma of the CNS","score":45,"mainType":"Miscellaneous Brain Tumor","tissue":"CNS/Brain","hierarchy":"BRAIN > MBT > MCHSCNS"},{"code":"MLYM","name":"Malignant Lymphoma","score":45,"mainType":"Miscellaneous Brain Tumor","tissue":"CNS/Brain","hierarchy":"BRAIN > MBT > MLYM"},{"code":"MT","name":"Malignant Tumor","score":45,"mainType":"Miscellaneous Brain Tumor","tissue":"CNS/Brain","hierarchy":"BRAIN > MBT > MT"},{"code":"PRNET","name":"Primary Neuroepithelial Tumor","score":45,"mainType":"Miscellaneous Brain Tumor","tissue":"CNS/Brain","hierarchy":"BRAIN > MBT > PRNET"},{"code":"ACPG","name":"Craniopharyngioma, Adamantinomatous Type","score":40,"mainType":"Sellar Tumor","tissue":"CNS/Brain","hierarchy":"BRAIN > SELT > ACPG"},{"code":"ACPP","name":"Atypical Choroid Plexus Papilloma","score":40,"mainType":"Choroid Plexus Tumor","tissue":"CNS/Brain","hierarchy":"BRAIN > CPT > ACPP"},{"code":"ADIFG","name":"Adult-Type Diffuse Glioma","score":40,"mainType":"Gliomas, Glioneuronal Tumors, and Neuronal Tumors","tissue":"CNS/Brain","hierarchy":"BRAIN > DIFG > ADIFG"},{"code":"AGNG","name":"Anaplastic Ganglioglioma","score":40,"mainType":"Glioma","tissue":"CNS/Brain","hierarchy":"BRAIN > ENCG > AGNG"},{"code":"AMBL","name":"Large Cell/Anaplastic Medulloblastoma","score":40,"mainType":"Embryonal Tumor","tissue":"CNS/Brain","hierarchy":"BRAIN > EMBT > AMBL"},{"code":"AMBLNOS","name":"Anaplastic Medulloblastoma, NOS","score":40,"mainType":"Large Cell/Anaplastic Medulloblastoma","tissue":"CNS/Brain","hierarchy":"BRAIN > EMBT > AMBL > AMBLNOS"},{"code":"AMBLNWS","name":"Anaplastic Medulloblastoma, Non-WNT, Non-SHH","score":40,"mainType":"Large Cell/Anaplastic Medulloblastoma","tissue":"CNS/Brain","hierarchy":"BRAIN > EMBT > AMBL > AMBLNWS"},{"code":"AMBLNWSG3","name":"Anaplastic Medulloblastoma, Group 3","score":40,"mainType":"Large Cell/Anaplastic Medulloblastoma","t … (1062 more chars)

▶ list_studies
{
 "search": "TCGA lung adenocarcinoma",
 "limit": 5
}

▶ list_studies
{
 "search": "TCGA glioblastoma",
 "limit": 5
}

◀ result
{"result":[{"cancer_study_identifier":"luad_tcga","name":"Lung Adenocarcinoma (TCGA, Firehose Legacy)","type_of_cancer_id":"luad","sample_count":586,"has_guide":false,"url":"https://www.cbioportal.org/study/summary?id=luad_tcga"},{"cancer_study_identifier":"luad_tcga_gdc","name":"Lung Adenocarcinoma (TCGA GDC, 2025)","type_of_cancer_id":"luad","sample_count":571,"has_guide":false,"url":"https://www.cbioportal.org/study/summary?id=luad_tcga_gdc"},{"cancer_study_identifier":"luad_tcga_pan_can_atlas_2018","name":"Lung Adenocarcinoma (TCGA, PanCancer Atlas)","type_of_cancer_id":"luad","sample_count":566,"has_guide":true,"url":"https://www.cbioportal.org/study/summary?id=luad_tcga_pan_can_atlas_2018"},{"cancer_study_identifier":"luad_tcga_pub","name":"Lung Adenocarcinoma (TCGA, Nature 2014)","type_of_cancer_id":"luad","sample_count":230,"has_guide":false,"url":"https://www.cbioportal.org/study/summary?id=luad_tcga_pub"}]}

◀ result
{"result":[{"cancer_study_identifier":"gbm_tcga","name":"Glioblastoma Multiforme (TCGA, Firehose Legacy)","type_of_cancer_id":"difg","sample_count":619,"has_guide":false,"url":"https://www.cbioportal.org/study/summary?id=gbm_tcga"},{"cancer_study_identifier":"gbm_tcga_gdc","name":"Glioblastoma Multiforme (TCGA GDC, 2025)","type_of_cancer_id":"difg","sample_count":611,"has_guide":false,"url":"https://www.cbioportal.org/study/summary?id=gbm_tcga_gdc"},{"cancer_study_identifier":"gbm_tcga_pan_can_atlas_2018","name":"Glioblastoma Multiforme (TCGA, PanCancer Atlas)","type_of_cancer_id":"difg","sample_count":592,"has_guide":true,"url":"https://www.cbioportal.org/study/summary?id=gbm_tcga_pan_can_atlas_2018"},{"cancer_study_identifier":"gbm_tcga_pub2013","name":"Glioblastoma (TCGA, Cell 2013)","type_of_cancer_id":"difg","sample_count":577,"has_guide":false,"url":"https://www.cbioportal.org/study/summary?id=gbm_tcga_pub2013"},{"cancer_study_identifier":"gbm_tcga_pub","name":"Glioblastoma (TCGA, Nature 2008)","type_of_cancer_id":"difg","sample_count":206,"has_guide":false,"url":"https://www.cbioportal.org/study/summary?id=gbm_tcga_pub"}]}

▶ clickhouse_run_select_query
{
 "query": "
-- EGFR mutations in lung adenocarcinoma vs glioblastoma
SELECT 
    cancer_study_identifier AS study,
    hugo_gene_symbol,
    altered_samples,
    profiled_samples,
    frequency_pct,
    total_mutation_events
FROM gene_mutation_frequency_in_studies(
    studies = ['luad_tcga_pan_can_atlas_2018', 'gbm_tcga_pan_can_atlas_2018'],
    gene = 'EGFR'
)
ORDER BY frequency_pct DESC;
",
 "max_rows": 10
}

◀ 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 identifier `cancer_study_identifier` in scope SELECT cancer_study_identifier AS study, hugo_gene_symbol, altered_samples, profiled_samples, frequency_pct, total_mutation_events FROM gene_mutation_frequency_in_studies(studies = ['luad_tcga_pan_can_atlas_2018', 'gbm_tcga_pan_can_atlas_2018'], gene = 'EGFR') ORDER BY frequency_pct DESC. (UNKNOWN_IDENTIFIER) (version 26.4.1.2359 (official build))\n"}

▶ clickhouse_run_select_query
{
 "query": "
-- EGFR mutations in lung adenocarcinoma
SELECT 
    'Lung Adenocarcinoma' AS cancer_type,
    hugo_gene_symbol,
    altered_samples,
    profiled_samples,
    frequency_pct,
    total_mutation_events
FROM gene_mutation_frequency_in_study(
    study = 'luad_tcga_pan_can_atlas_2018',
    gene = 'EGFR'
)
UNION ALL
-- EGFR mutations in glioblastoma
SELECT 
    'Glioblastoma' AS cancer_type,
    hugo_gene_symbol,
    altered_samples,
    profiled_samples,
    frequency_pct,
    total_mutation_events
FROM gene_mutation_frequency_in_study(
    study = 'gbm_tcga_pan_can_atlas_2018',
    gene = 'EGFR'
)
ORDER BY cancer_type;
",
 "max_rows": 10
}

◀ 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 identifier `hugo_gene_symbol` in scope SELECT 'Lung Adenocarcinoma' AS cancer_type, hugo_gene_symbol, altered_samples, profiled_samples, frequency_pct, total_mutation_events FROM gene_mutation_frequency_in_study(study = 'luad_tcga_pan_can_atlas_2018', gene = 'EGFR'). (UNKNOWN_IDENTIFIER) (version 26.4.1.2359 (official build))\n"}

▶ clickhouse_run_select_query
{
 "query": "
SELECT *
FROM gene_mutation_frequency_in_study(
    study = 'luad_tcga_pan_can_atlas_2018',
    gene = 'EGFR'
)
LIMIT 5;
",
 "max_rows": 10
}

◀ result
{"rows":[{"cancer_type":"Non-Small Cell Lung Cancer","altered_samples":70,"profiled_samples":566,"frequency_pct":12.4}]}

▶ clickhouse_run_select_query
{
 "query": "
-- EGFR mutations in lung adenocarcinoma
SELECT 
    'Lung Adenocarcinoma (TCGA Pan-Cancer Atlas)' AS study,
    cancer_type,
    altered_samples,
    profiled_samples,
    frequency_pct
FROM gene_mutation_frequency_in_study(
    study = 'luad_tcga_pan_can_atlas_2018',
    gene = 'EGFR'
)
UNION ALL
-- EGFR mutations in glioblastoma
SELECT 
    'Glioblastoma (TCGA Pan-Cancer Atlas)' AS study,
    cancer_type,
    altered_samples,
    profiled_samples,
    frequency_pct
FROM gene_mutation_frequency_in_study(
    study = 'gbm_tcga_pan_can_atlas_2018',
    gene = 'EGFR'
);
",
 "max_rows": 10
}

◀ result
{"rows":[{"study":"Lung Adenocarcinoma (TCGA Pan-Cancer Atlas)","cancer_type":"Non-Small Cell Lung Cancer","altered_samples":70,"profiled_samples":566,"frequency_pct":12.4},{"study":"Glioblastoma (TCGA Pan-Cancer Atlas)","cancer_type":"Glioblastoma","altered_samples":94,"profiled_samples":397,"frequency_pct":23.7}]}

▶ clickhouse_run_select_query
{
 "query": "
-- Top EGFR mutation variants in lung adenocarcinoma
SELECT 
    'Lung Adenocarcinoma' AS cancer_type,
    mutation_variant,
    mutation_type,
    altered_samples,
    profiled_samples,
    frequency_pct
FROM gene_mutation_variants_in_study(
    study = 'luad_tcga_pan_can_atlas_2018',
    gene = 'EGFR'
)
LIMIT 10;
",
 "max_rows": 20
}

◀ result
{"rows":[{"cancer_type":"Lung Adenocarcinoma","mutation_variant":"L858R","mutation_type":"Missense_Mutation","altered_samples":23,"profiled_samples":566,"frequency_pct":4.1},{"cancer_type":"Lung Adenocarcinoma","mutation_variant":"E746_A750del","mutation_type":"In_Frame_Del","altered_samples":16,"profiled_samples":566,"frequency_pct":2.8},{"cancer_type":"Lung Adenocarcinoma","mutation_variant":"E709_T710delinsD","mutation_type":"In_Frame_Del","altered_samples":3,"profiled_samples":566,"frequency_pct":0.5},{"cancer_type":"Lung Adenocarcinoma","mutation_variant":"L861Q","mutation_type":"Missense_Mutation","altered_samples":3,"profiled_samples":566,"frequency_pct":0.5},{"cancer_type":"Lung Adenocarcinoma","mutation_variant":"G719A","mutation_type":"Missense_Mutation","altered_samples":2,"profiled_samples":566,"frequency_pct":0.4},{"cancer_type":"Lung Adenocarcinoma","mutation_variant":"L62R","mutation_type":"Missense_Mutation","altered_samples":2,"profiled_samples":566,"frequency_pct":0.4},{"cancer_type":"Lung Adenocarcinoma","mutation_variant":"L747_A750delinsP","mutation_type":"In_Frame_Del","altered_samples":2,"profiled_samples":566,"frequency_pct":0.4},{"cancer_type":"Lung Adenocarcinoma","mutation_variant":"L747_T751del","mutation_type":"In_Frame_Del","altered_samples":2,"profiled_samples":566,"frequency_pct":0.4},{"cancer_type":"Lung Adenocarcinoma","mutation_variant":"S768I","mutation_type":"Missense_Mutation","altered_samples":2,"profiled_samples":566,"frequency_pct":0.4},{"cancer_type":"Lung Adenocarcinoma","mutation_variant":"T790M","mutation_type":"Missense_Mutation","altered_samples":2,"profiled_samples":566,"frequency_pct":0.4}]}

▶ clickhouse_run_select_query
{
 "query": "
-- Top EGFR mutation variants in glioblastoma
SELECT 
    'Glioblastoma' AS cancer_type,
    mutation_variant,
    mutation_type,
    altered_samples,
    profiled_samples,
    frequency_pct
FROM gene_mutation_variants_in_study(
    study = 'gbm_tcga_pan_can_atlas_2018',
    gene = 'EGFR'
)
LIMIT 10;
",
 "max_rows": 20
}

◀ result
{"rows":[{"cancer_type":"Glioblastoma","mutation_variant":"A289V","mutation_type":"Missense_Mutation","altered_samples":16,"profiled_samples":397,"frequency_pct":4},{"cancer_type":"Glioblastoma","mutation_variant":"G598V","mutation_type":"Missense_Mutation","altered_samples":15,"profiled_samples":397,"frequency_pct":3.8},{"cancer_type":"Glioblastoma","mutation_variant":"A289T","mutation_type":"Missense_Mutation","altered_samples":6,"profiled_samples":397,"frequency_pct":1.5},{"cancer_type":"Glioblastoma","mutation_variant":"R222C","mutation_type":"Missense_Mutation","altered_samples":6,"profiled_samples":397,"frequency_pct":1.5},{"cancer_type":"Glioblastoma","mutation_variant":"A289D","mutation_type":"Missense_Mutation","altered_samples":5,"profiled_samples":397,"frequency_pct":1.3},{"cancer_type":"Glioblastoma","mutation_variant":"V774M","mutation_type":"Missense_Mutation","altered_samples":5,"profiled_samples":397,"frequency_pct":1.3},{"cancer_type":"Glioblastoma","mutation_variant":"R108K","mutation_type":"Missense_Mutation","altered_samples":4,"profiled_samples":397,"frequency_pct":1},{"cancer_type":"Glioblastoma","mutation_variant":"G63R","mutation_type":"Missense_Mutation","altered_samples":3,"profiled_samples":397,"frequency_pct":0.8},{"cancer_type":"Glioblastoma","mutation_variant":"H304Y","mutation_type":"Missense_Mutation","altered_samples":3,"profiled_samples":397,"frequency_pct":0.8},{"cancer_type":"Glioblastoma","mutation_variant":"R252C","mutation_type":"Missense_Mutation","altered_samples":3,"profiled_samples":397,"frequency_pct":0.8}]}

▶ resolve_and_route
{
 "studyIds": [
  "luad_tcga_pan_can_atlas_2018",
  "gbm_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":"gbm_tcga_pan_can_atlas_2018","name":"Glioblastoma Multif … (2394 more chars)

▶ navigate_to_results_view
{
 "studyIds": [
  "luad_tcga_pan_can_atlas_2018"
 ],
 "genes": [
  "EGFR"
 ],
 "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=EGFR&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=EGFR&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":["EGFR"],"caseSetId":"luad_tcga_pan_can_atlas_2018_all","pageDescription":"Detailed mutation table with lollipop plot showing mutation positions, types, and frequencies for queried genes."}}

▶ navigate_to_results_view
{
 "studyIds": [
  "gbm_tcga_pan_can_atlas_2018"
 ],
 "genes": [
  "EGFR"
 ],
 "tab": "mutations"
}

◀ result
{"success":true,"message":"Navigating to https://www.cbioportal.org/results/mutations?cancer_study_list=gbm_tcga_pan_can_atlas_2018&gene_list=EGFR&case_set_id=gbm_tcga_pan_can_atlas_2018_all","url":"https://www.cbioportal.org/results/mutations?cancer_study_list=gbm_tcga_pan_can_atlas_2018&gene_list=EGFR&case_set_id=gbm_tcga_pan_can_atlas_2018_all","data":{"studyIds":["gbm_tcga_pan_can_atlas_2018"],"studies":[{"studyId":"gbm_tcga_pan_can_atlas_2018","name":"Glioblastoma Multiforme (TCGA, PanCancer Atlas)","sampleCount":592}],"genes":["EGFR"],"caseSetId":"gbm_tcga_pan_can_atlas_2018_all","pageDescription":"Detailed mutation table with lollipop plot showing mutation positions, types, and frequencies for queried genes."}}

═ answer (success)
## EGFR Mutations: Lung Adenocarcinoma vs Glioblastoma

### Summary Comparison

| Cancer Type | Study | Mutated Samples | Profiled Samples | Frequency |
|---|---|---|---|---|
| **Lung Adenocarcinoma** | TCGA Pan-Cancer Atlas | 70 | 566 | **12.4%** |
| **Glioblastoma** | TCGA Pan-Cancer Atlas | 94 | 397 | **23.7%** |

**Key Finding:** EGFR mutations are nearly **2× more frequent in glioblastoma (23.7%) than in lung adenocarcinoma (12.4%)**, despite lung cancer being classically associated with EGFR-driven mutations.

---

### Mutational Spectrum

**Lung Adenocarcinoma** — Dominated by **classic activating mutations**:
- **L858R** (23/566, 4.1%) — in-frame missense mutation, TKI-sensitive
- **E746_A750del** (16/566, 2.8%) — exon 19 deletion, TKI-sensitive
- Other variants: L861Q, G719A, E709_T710delinsD (all <1% each)

**Glioblastoma** — Dominated by **extracellular domain (ECD) variants**:
- **A289V** (16/397, 4.0%) — ECD missense mutation
- **G598V** (15/397, 3.8%) — ECD missense mutation
- **A289T, R222C** (6 samples each, 1.5%) — ECD region
- Notable: Primarily missense changes in the extracellular domain, not the canonical kinase-domain variants seen in lung cancer

---

### Biologic Interpretation

1. **Different mutation hotspots:** Lung adenocarcinoma EGFR mutations cluster in the **tyrosine kinase domain** (L858R, exon 19 deletions), which are TKI-responsive. Glioblastoma mutations are spread across the **extracellular domain**, a pattern consistent with truncating/constitutive-activation EGFR variants (like EGFRvIII) common in GBM.

2. **Clinical implications:** The TKI-sensitive mutations in lung adenocarcinoma (L858R, exon 19 del) are druggable targets for EGFR inhibitors. Glioblastoma's ECD-domain mutations may represent a different biological process and may have distinct response profiles.

---

### Explore the Data

**Lung Adenocarcinoma EGFR Mutations:**  
[View mutation details, lollipop plot, and patient samples](https://www.cbioportal.org/results/mutations?cancer_study_list=luad_tcga_pan_can_atlas_2018&gene_list=EGFR&case_set_id=luad_tcga_pan_can_atlas_2018_all)

**Glioblastoma EGFR Mutations:**  
[View mutation details, lollipop plot, and patient samples](https://www.cbioportal.org/results/mutations?cancer_study_list=gbm_tcga_pan_can_atlas_2018&gene_list=EGFR&case_set_id=gbm_tcga_pan_can_atlas_2018_all)