Q (sonnet): 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"
}

◀ 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_impact_50k_2026","name":"MSK-IMPACT 50K Clinical Sequencing Cohort (MSK, Cancer Cell 2026)","type_of_cancer_id":"mixed","sample_count":54331,"has_guide":false,"url":"https://www.cbioportal.org/study/summary?id=msk_impact_50k_2026"},{"cancer_study_identifier":"msk_ch_2023","name":"Cancer Therapy and Clonal Hematopoiesis (MSK, Blood Adv 2023)","type_of_cancer_id":"mixed","sample_count":42714,"has_guide":false,"url":"https://www.cbioportal.org/study/summary?id=msk_ch_2023"},{"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"},{"cancer_study_identifier":"msk_ch_2020","name":"Cancer Therapy and Clonal Hematopoiesis (MSK, Nat Genet 2020)","type_of_cancer_id":"mixed","sample_count":24146,"has_guide":false,"url":"https://www.cbioportal.org/study/summary?id=msk_ch_2020"},{"cancer_study_identifier":"msk_impact_2017","name":"MSK-IMPACT Clinical Sequencing Cohort (MSK, Nat Med 2017)","type_of_cancer_id":"mixed","sample_count":10945,"has_guide":false,"url":"https://www.cbioportal.org/study/summary?id=msk_impact_2017"},{"cancer_study_identifier":"crc_msk_2026","name":"Colorectal Adenocarcinoma (MSK, 2026)","type_of_cancer_id":"read","sample_count":7237,"has_guide":false,"url":"https://www.cbioportal.org/study/summary?id=crc_msk_2026"},{"cancer_study_identifier":"breast_msk_2026","name":"CCNE1 Amplifications in Breast Cancer (MSK, 2026)","type_of_cancer_id":"breast","sample_count":6318,"has_guide":false,"url":"https://www.cbioportal.org/study/summary?id=breast_msk_2026"},{"cancer_study_identifier":"pancan_mimsi_msk_2024","name":"Mixed Tumors - MiMSI Cohort (MSK, Nat Commun 2024)","type_of_cancer_id":"mixed","sample_count":5033,"has_guide":false,"url":"https://www.cbioportal.org/study/summary?id=pancan_mimsi_msk_2024"},{"cancer_study_identifier":"breast_msk_2025","name":"Breast Cancer (MSK, Nat Genet 2025)","type_of_cancer_id":"brca","sample_count":3879,"has_guide":false,"url":"https://www.cbioportal.org/study/summary?id=breast_msk_2025"},{"cancer_study_identifier":"mycf_msk_2026","name":"MYC Family Amplifications in MSK-IMPACT Solid Tumors (MSK, 2026)","type_of_cancer_id":"mixed","sample_count":3442,"has_guide":false,"url":"https://www.cbioportal.org/study/summary?id=mycf_msk_2026"},{"cancer_study_identifier":"heme_msk_impact_2022","name":"MSK-IMPACT Heme Tumors (MSK, 2022)","type_of_cancer_id":"mixed","sample_count":2383,"has_guide":false,"url":"https://www.cbioportal.org/study/summary?id=heme_msk_impact_2022"},{"cancer_study_identifier":"pdac_msk_2024","name":"Pancreatic Adenocarcinoma (MSK, Nat Med 2024)","type_of_cancer_id":"pancreas","sample_count":2336,"has_guide":false,"url":"https://www.cbioportal.org/study/summary?id=pdac_msk_2024"},{"cancer_study_identifier":"prostate_msk_2024","name":"Prostate Cancer (MSK, Clin Cancer Res 2024)","type_of_cancer_id" … (1829 more chars)

▶ clickhouse_run_select_query
{
 "query": "SELECT * FROM gene_mutation_frequency_by_cancer_type(preference = 'large_genomic_cohort', 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":"Colorectal Cancer","altered_samples":135,"profiled_samples":5277,"frequency_pct":2.6},{"cancer_type":"Cancer of Unknown Primary","altered_samples":41,"profiled_samples":1581,"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":"Esophagogastric Cancer","altered_samples":38,"profiled_samples":1834,"frequency_pct":2.1},{"cancer_type":"Anal Cancer","altered_samples":3,"profiled_samples":143,"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":"Prostate Cancer","altered_samples":30,"profiled_samples":3324,"frequency_pct":0.9},{"cancer_type":"Cervical Cancer","altered_samples":3,"profiled_samples":351,"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":"Thyroid Cancer","altered_samples":6,"profiled_samples":867,"frequency_pct":0.7},{"cancer_type":"Appendiceal Cancer","altered_samples":2,"profiled_samples":274,"frequency_pct":0.7},{"cancer_type":"Soft Tissue Sarcoma","altered_samples":14,"profiled_samples":2307,"frequency_pct":0.6},{"cancer_type":"Pancreatic Cancer","altered_samples":16,"profiled_samples":2851,"frequency_pct":0.6},{"cancer_typ … (404 more chars)

═ answer (success)
## EGFR Mutation Frequency Across Cancer Types — MSK-IMPACT 50K

Study: [MSK-IMPACT 50K Clinical Sequencing Cohort (MSK, Cancer Cell 2026)](https://www.cbioportal.org/study/summary?id=msk_impact_50k_2026) (54,331 samples). Counting unit: **samples** (this is a targeted-panel clinical cohort, one sample per typical case). Denominators are gene-specific profiled samples (only cancer types with ≥50 EGFR-profiled samples shown).

| Cancer Type | Altered / Profiled | 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% |
| Endometrial Cancer | 105 / 2,445 | 4.3% |
| Bladder Cancer | 87 / 2,526 | 3.4% |
| Colorectal Cancer | 135 / 5,277 | 2.6% |
| Cancer of Unknown Primary | 41 / 1,581 | 2.6% |
| Esophagogastric Cancer | 38 / 1,834 | 2.1% |
| Head and Neck Cancer | 12 / 657 | 1.8% |
| Breast Cancer | 100 / 6,807 | 1.5% |
| Hepatobiliary Cancer | 17 / 1,431 | 1.2% |
| Prostate Cancer | 30 / 3,324 | 0.9% |
| Ovarian Cancer | 18 / 2,140 | 0.8% |
| Germ Cell Tumor | 6 / 725 | 0.8% |
| Thyroid Cancer | 6 / 867 | 0.7% |
| Soft Tissue Sarcoma | 14 / 2,307 | 0.6% |
| Pancreatic Cancer | 16 / 2,851 | 0.6% |
| Renal Cell Carcinoma | 7 / 1,209 | 0.6% |
| Bone Cancer | 1 / 590 | 0.2% |

(Several smaller categories with 50–350 profiled samples — e.g. Small Bowel, Anal, Adrenocortical, Ampullary, Uterine Sarcoma, Salivary Gland, Cervical, Sellar Tumor, Appendiceal, GIST, Peripheral Nervous System cancers — are omitted here for brevity; each had ≤5 altered samples. Ask if you'd like the full list.)

**Key finding:** EGFR mutations are overwhelmingly concentrated in Non-Small Cell Lung Cancer (26.2%) and Glioma (15.2%), consistent with EGFR's established roles as a targetable oncogenic driver in lung adenocarcinoma and as an amplification/mutation target in glioblastoma. Frequencies drop off sharply outside these two cancer types.

You can explore this interactively, including OncoPrint and mutation-type breakdowns, here:

[View EGFR Alterations — MSK-IMPACT 50K (Results View)](https://www.cbioportal.org/results/oncoprint?cancer_study_list=msk_impact_50k_2026&gene_list=EGFR&tab_index=tab_visualize)

[Browse the MSK-IMPACT 50K Cohort (Study View)](https://www.cbioportal.org/study/summary?id=msk_impact_50k_2026)