Q (sonnet): What are the most frequently altered genes in KRAS wild-type lung adenocarcinoma patients?

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

▶ list_studies
{
 "search": "lung adenocarcinoma"
}

◀ 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_met_2021","name":"MSK MetTropism (MSK, Cell 2021)","type_of_cancer_id":"mixed","sample_count":25775,"has_guide":false,"url":"https://www.cbioportal.org/study/summary?id=msk_met_2021"},{"cancer_study_identifier":"luad_mskcc_2023_met_organotropism","name":"Lung Adenocarcinoma Met Organotropism (MSK, Cancer Cell 2023)","type_of_cancer_id":"luad","sample_count":2653,"has_guide":false,"url":"https://www.cbioportal.org/study/summary?id=luad_mskcc_2023_met_organotropism"},{"cancer_study_identifier":"lung_msk_2017","name":"Non-Small Cell Cancer (MSK, Cancer Discov 2017)","type_of_cancer_id":"luad","sample_count":915,"has_guide":false,"url":"https://www.cbioportal.org/study/summary?id=lung_msk_2017"},{"cancer_study_identifier":"luad_mskcc_2020","name":"Lung Adenocarcinoma (MSK, J Thorac Oncol 2020)","type_of_cancer_id":"luad","sample_count":604,"has_guide":false,"url":"https://www.cbioportal.org/study/summary?id=luad_mskcc_2020"},{"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_msk_npjpo_2021","name":"Lung Adenocarcinoma (MSK, NPJ Precision Oncology 2021)","type_of_cancer_id":"luad","sample_count":426,"has_guide":false,"url":"https://www.cbioportal.org/study/summary?id=luad_msk_npjpo_2021"},{"cancer_study_identifier":"luad_oncosg_2020","name":"Lung Adenocarcinoma (OncoSG, Nat Genet 2020)","type_of_cancer_id":"luad","sample_count":305,"has_guide":false,"url":"https://www.cbioportal.org/study/summary?id=luad_oncosg_2020"},{"cancer_study_identifier":"lung_msk_mind_2020","name":"Lung Adenocarcinoma (MSK Mind,Nature Cancer 2022)","type_of_cancer_id":"lung","sample_count":247,"has_guide":false,"url":"https://www.cbioportal.org/study/summary?id=lung_msk_mind_2020"},{"cancer_study_identifier":"luad_cptac_gdc","name":"Lung Adenocarcinoma (CPTAC GDC, 2025)","type_of_cancer_id":"luad","sample_count":241,"has_guide":false,"url":"https://www.cbioportal.org/study/summary?id=luad_cptac_gdc"},{"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"},{"cancer_study_identifier":"luad_mskimpact_2021","name":"Lung Adenocarcinoma (MSK, 2021)","type_of_cancer_id":"luad","sample_count":186,"has_guide":false, … (1174 more chars)

▶ clickhouse_run_select_query
{
 "query": "SELECT * FROM co_altered_genes_in_study(study = 'luad_tcga_pan_can_atlas_2018', gene = 'KRAS', top_n = 20)"
}

◀ result
{"rows":[{"hugo_gene_symbol":"TP53","mutant_altered":62,"mutant_profiled":168,"mutant_pct":36.9,"wildtype_altered":233,"wildtype_profiled":398,"wildtype_pct":58.5,"pct_difference":-21.6},{"hugo_gene_symbol":"EGFR","mutant_altered":1,"mutant_profiled":168,"mutant_pct":0.6,"wildtype_altered":69,"wildtype_profiled":398,"wildtype_pct":17.3,"pct_difference":-16.7},{"hugo_gene_symbol":"STK11","mutant_altered":38,"mutant_profiled":168,"mutant_pct":22.6,"wildtype_altered":37,"wildtype_profiled":398,"wildtype_pct":9.3,"pct_difference":13.3},{"hugo_gene_symbol":"ATM","mutant_altered":28,"mutant_profiled":168,"mutant_pct":16.7,"wildtype_altered":19,"wildtype_profiled":398,"wildtype_pct":4.8,"pct_difference":11.9},{"hugo_gene_symbol":"MUC16","mutant_altered":84,"mutant_profiled":168,"mutant_pct":50,"wildtype_altered":158,"wildtype_profiled":398,"wildtype_pct":39.7,"pct_difference":10.3},{"hugo_gene_symbol":"NF1","mutant_altered":8,"mutant_profiled":168,"mutant_pct":4.8,"wildtype_altered":58,"wildtype_profiled":398,"wildtype_pct":14.6,"pct_difference":-9.8},{"hugo_gene_symbol":"CSMD1","mutant_altered":48,"mutant_profiled":168,"mutant_pct":28.6,"wildtype_altered":77,"wildtype_profiled":398,"wildtype_pct":19.3,"pct_difference":9.3},{"hugo_gene_symbol":"CNTNAP2","mutant_altered":32,"mutant_profiled":168,"mutant_pct":19,"wildtype_altered":39,"wildtype_profiled":398,"wildtype_pct":9.8,"pct_difference":9.2},{"hugo_gene_symbol":"RIMS2","mutant_altered":32,"mutant_profiled":168,"mutant_pct":19,"wildtype_altered":40,"wildtype_profiled":398,"wildtype_pct":10.1,"pct_difference":8.9},{"hugo_gene_symbol":"LRP1B","mutant_altered":69,"mutant_profiled":168,"mutant_pct":41.1,"wildtype_altered":132,"wildtype_profiled":398,"wildtype_pct":33.2,"pct_difference":7.9},{"hugo_gene_symbol":"LRRC7","mutant_altered":34,"mutant_profiled":168,"mutant_pct":20.2,"wildtype_altered":49,"wildtype_profiled":398,"wildtype_pct":12.3,"pct_difference":7.9},{"hugo_gene_symbol":"TNR","mutant_altered":19,"mutant_profiled":168,"mutant_pct":11.3,"wildtype_altered":76,"wildtype_profiled":398,"wildtype_pct":19.1,"pct_difference":-7.8},{"hugo_gene_symbol":"BRAF","mutant_altered":3,"mutant_profiled":168,"mutant_pct":1.8,"wildtype_altered":38,"wildtype_profiled":398,"wildtype_pct":9.5,"pct_difference":-7.7},{"hugo_gene_symbol":"RP1L1","mutant_altered":37,"mutant_profiled":168,"mutant_pct":22,"wildtype_altered":60,"wildtype_profiled":398,"wildtype_pct":15.1,"pct_difference":6.9},{"hugo_gene_symbol":"ZFHX4","mutant_altered":63,"mutant_profiled":168,"mutant_pct":37.5,"wildtype_altered":122,"wildtype_profiled":398,"wildtype_pct":30.7,"pct_difference":6.8},{"hugo_gene_symbol":"HECTD4","mutant_altered":18,"mutant_profiled":168,"mutant_pct":10.7,"wildtype_altered":16,"wildtype_profiled":398,"wildtype_pct":4,"pct_difference":6.7},{"hugo_gene_symbol":"KMT2C","mutant_altered":15,"mutant_profiled":168,"mutant_pct":8.9,"wildtype_altered":62,"wildtype_profiled":398,"wildtype_pct":15.6,"pct_difference":-6.7},{"hugo_gene_ … (513 more chars)

▶ clickhouse_run_select_query
{
 "query": "SELECT * FROM co_altered_genes_in_study(study = 'luad_tcga_pan_can_atlas_2018', gene = 'KRAS', top_n = 40)
ORDER BY wildtype_pct DESC
LIMIT 15"
}

◀ result
{"rows":[{"hugo_gene_symbol":"TP53","mutant_altered":62,"mutant_profiled":168,"mutant_pct":36.9,"wildtype_altered":233,"wildtype_profiled":398,"wildtype_pct":58.5,"pct_difference":-21.6},{"hugo_gene_symbol":"MUC16","mutant_altered":84,"mutant_profiled":168,"mutant_pct":50,"wildtype_altered":158,"wildtype_profiled":398,"wildtype_pct":39.7,"pct_difference":10.3},{"hugo_gene_symbol":"LRP1B","mutant_altered":69,"mutant_profiled":168,"mutant_pct":41.1,"wildtype_altered":132,"wildtype_profiled":398,"wildtype_pct":33.2,"pct_difference":7.9},{"hugo_gene_symbol":"ZFHX4","mutant_altered":63,"mutant_profiled":168,"mutant_pct":37.5,"wildtype_altered":122,"wildtype_profiled":398,"wildtype_pct":30.7,"pct_difference":6.8},{"hugo_gene_symbol":"CSMD1","mutant_altered":48,"mutant_profiled":168,"mutant_pct":28.6,"wildtype_altered":77,"wildtype_profiled":398,"wildtype_pct":19.3,"pct_difference":9.3},{"hugo_gene_symbol":"TNR","mutant_altered":19,"mutant_profiled":168,"mutant_pct":11.3,"wildtype_altered":76,"wildtype_profiled":398,"wildtype_pct":19.1,"pct_difference":-7.8},{"hugo_gene_symbol":"EGFR","mutant_altered":1,"mutant_profiled":168,"mutant_pct":0.6,"wildtype_altered":69,"wildtype_profiled":398,"wildtype_pct":17.3,"pct_difference":-16.7},{"hugo_gene_symbol":"ZNF804A","mutant_altered":19,"mutant_profiled":168,"mutant_pct":11.3,"wildtype_altered":69,"wildtype_profiled":398,"wildtype_pct":17.3,"pct_difference":-6},{"hugo_gene_symbol":"AHNAK2","mutant_altered":18,"mutant_profiled":168,"mutant_pct":10.7,"wildtype_altered":65,"wildtype_profiled":398,"wildtype_pct":16.3,"pct_difference":-5.6},{"hugo_gene_symbol":"KMT2C","mutant_altered":15,"mutant_profiled":168,"mutant_pct":8.9,"wildtype_altered":62,"wildtype_profiled":398,"wildtype_pct":15.6,"pct_difference":-6.7},{"hugo_gene_symbol":"RP1L1","mutant_altered":37,"mutant_profiled":168,"mutant_pct":22,"wildtype_altered":60,"wildtype_profiled":398,"wildtype_pct":15.1,"pct_difference":6.9},{"hugo_gene_symbol":"PKHD1","mutant_altered":15,"mutant_profiled":168,"mutant_pct":8.9,"wildtype_altered":59,"wildtype_profiled":398,"wildtype_pct":14.8,"pct_difference":-5.9},{"hugo_gene_symbol":"NF1","mutant_altered":8,"mutant_profiled":168,"mutant_pct":4.8,"wildtype_altered":58,"wildtype_profiled":398,"wildtype_pct":14.6,"pct_difference":-9.8},{"hugo_gene_symbol":"LRRC7","mutant_altered":34,"mutant_profiled":168,"mutant_pct":20.2,"wildtype_altered":49,"wildtype_profiled":398,"wildtype_pct":12.3,"pct_difference":7.9},{"hugo_gene_symbol":"PKD1L1","mutant_altered":10,"mutant_profiled":168,"mutant_pct":6,"wildtype_altered":45,"wildtype_profiled":398,"wildtype_pct":11.3,"pct_difference":-5.3}]}

▶ resolve_and_route
{
 "studyIds": [
  "luad_tcga_pan_can_atlas_2018"
 ]
}

◀ result
{"success":true,"message":"Found 1 study. Use the metadata to call the appropriate navigation tool(s).","data":{"totalCount":1,"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"]}}]}}

▶ get_studyviewfilter_options
{
 "studyId": "luad_tcga_pan_can_atlas_2018",
 "geneSpecificQueries": [
  {
   "hugoGeneSymbol": "KRAS",
   "profileType": "mutations"
  }
 ]
}

◀ result
{"success":true,"message":"Successfully retrieved StudyView filter options","data":{"studyId":"luad_tcga_pan_can_atlas_2018","geneSpecificCounts":[{"hugoGeneSymbol":"KRAS","profileType":"mutations","counts":[{"value":"Missense_Mutation","label":"Missense Mutation","count":171},{"value":"Nonsense_Mutation","label":"Nonsense Mutation","count":1}]}]}}

▶ navigate_to_study_view
{
 "studyIds": [
  "luad_tcga_pan_can_atlas_2018"
 ],
 "filterJson": {
  "mutationDataFilters": [
   {
    "hugoGeneSymbol": "KRAS",
    "profileType": "mutations",
    "categorization": "MUTATED",
    "values": [
     [
      {
       "value": "NOT_MUTATED"
      }
     ]
    ]
   }
  ]
 }
}

◀ result
{"success":true,"message":"Navigating to https://www.cbioportal.org/study/summary?id=luad_tcga_pan_can_atlas_2018#filterJson=%7B%22mutationDataFilters%22%3A%5B%7B%22categorization%22%3A%22MUTATED%22%2C%22hugoGeneSymbol%22%3A%22KRAS%22%2C%22profileType%22%3A%22mutations%22%2C%22values%22%3A%5B%5B%7B%22value%22%3A%22NOT_MUTATED%22%7D%5D%5D%7D%5D%7D","url":"https://www.cbioportal.org/study/summary?id=luad_tcga_pan_can_atlas_2018#filterJson=%7B%22mutationDataFilters%22%3A%5B%7B%22categorization%22%3A%22MUTATED%22%2C%22hugoGeneSymbol%22%3A%22KRAS%22%2C%22profileType%22%3A%22mutations%22%2C%22values%22%3A%5B%5B%7B%22value%22%3A%22NOT_MUTATED%22%7D%5D%5D%7D%5D%7D","data":{"studyIds":["luad_tcga_pan_can_atlas_2018"],"studies":[{"studyId":"luad_tcga_pan_can_atlas_2018","name":"Lung Adenocarcinoma (TCGA, PanCancer Atlas)","sampleCount":566}],"tab":"summary","hasFilters":true,"hasPlotsConfig":false,"pageDescription":"Overview of all study data displayed as interactive charts summarizing available clinical and genomic data. Click within a chart to filter. Additional charts may be available in the Charts menu."}}

▶ navigate_to_results_view
{
 "studyIds": [
  "luad_tcga_pan_can_atlas_2018"
 ],
 "genes": [
  "KRAS",
  "TP53",
  "MUC16",
  "LRP1B",
  "ZFHX4",
  "CSMD1",
  "TNR",
  "EGFR",
  "KMT2C",
  "NF1",
  "RP1L1"
 ],
 "tab": "oncoprint",
 "studyViewFilter": {
  "mutationDataFilters": [
   {
    "hugoGeneSymbol": "KRAS",
    "profileType": "mutations",
    "categorization": "MUTATED",
    "values": [
     [
      {
       "value": "NOT_MUTATED"
      }
     ]
    ]
   }
  ]
 }
}

◀ result
{"success":true,"message":"Navigating to https://www.cbioportal.org/results/oncoprint?session_id=6ab5cf8ae497aad53593c281","url":"https://www.cbioportal.org/results/oncoprint?session_id=6ab5cf8ae497aad53593c281","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":["KRAS","TP53","MUC16","LRP1B","ZFHX4","CSMD1","TNR","EGFR","KMT2C","NF1","RP1L1"],"filteredSampleCount":398,"caseSetId":"-1","sessionId":"6ab5cf8ae497aad53593c281","studyViewUrl":"https://www.cbioportal.org/study?id=luad_tcga_pan_can_atlas_2018#filterJson=%7B%22mutationDataFilters%22%3A%5B%7B%22hugoGeneSymbol%22%3A%22KRAS%22%2C%22profileType%22%3A%22mutations%22%2C%22categorization%22%3A%22MUTATED%22%2C%22values%22%3A%5B%5B%7B%22value%22%3A%22NOT_MUTATED%22%7D%5D%5D%7D%5D%7D","pageDescription":"Visual summary of alterations in queried genes across samples."}}

═ answer (success)
## Most Frequently Mutated Genes in KRAS Wild-Type Lung Adenocarcinoma

**Cohort:** [Lung Adenocarcinoma (TCGA, PanCancer Atlas)](https://www.cbioportal.org/study/summary?id=luad_tcga_pan_can_atlas_2018) — 398 samples with no KRAS mutation, out of 566 profiled for KRAS (168 KRAS-mutant samples excluded). Counting unit: samples. This reflects point mutations only (no CNA/SV).

| Gene | Altered / Profiled (KRAS-WT) | Frequency |
|---|---|---|
| **TP53** | 233 / 398 | **58.5%** |
| **MUC16** | 158 / 398 | **39.7%** |
| **LRP1B** | 132 / 398 | **33.2%** |
| **ZFHX4** | 122 / 398 | **30.7%** |
| **CSMD1** | 77 / 398 | **19.3%** |
| **TNR** | 76 / 398 | **19.1%** |
| **EGFR** | 69 / 398 | **17.3%** |
| **ZNF804A** | 69 / 398 | **17.3%** |
| **AHNAK2** | 65 / 398 | **16.3%** |
| **KMT2C** | 62 / 398 | **15.6%** |

A few caveats worth noting:
- TP53 dominates regardless of KRAS status (36.9% in KRAS-mutant vs 58.5% in KRAS-WT) — it's the single most common driver-associated alteration in lung adenocarcinoma overall.
- MUC16, LRP1B, CSMD1, and TNR are very large genes that accumulate passenger mutations at high rates in most lung adenocarcinomas (smoking-associated high tumor mutational burden) — their frequency here isn't necessarily specific to KRAS-WT biology.
- EGFR is notably enriched in the KRAS-WT group (17.3%) versus almost absent in KRAS-mutant tumors (0.6%), consistent with the well-known mutual exclusivity between KRAS and EGFR driver mutations in lung adenocarcinoma — though I have not run a statistical test to confirm significance of that exclusivity here.
- This is mutation-only ranking; it doesn't include copy-number amplifications/deletions or structural variants (e.g., ALK/ROS1 fusions, MET amplification), which are also common oncogenic drivers in KRAS-WT LUAD but not counted in this table.

**Explore further:**
- [Study View filtered to KRAS wild-type samples (398 patients)](https://www.cbioportal.org/study/summary?id=luad_tcga_pan_can_atlas_2018#filterJson=%7B%22mutationDataFilters%22%3A%5B%7B%22categorization%22%3A%22MUTATED%22%2C%22hugoGeneSymbol%22%3A%22KRAS%22%2C%22profileType%22%3A%22mutations%22%2C%22values%22%3A%5B%5B%7B%22value%22%3A%22NOT_MUTATED%22%7D%5D%5D%7D%5D%7D) — browse clinical and genomic distributions in this subgroup.
- [OncoPrint of top genes in KRAS-WT samples](https://www.cbioportal.org/results/oncoprint?session_id=6ab5cf8ae497aad53593c281) — visualize co-occurrence and mutual exclusivity patterns across TP53, EGFR, MUC16, LRP1B, ZFHX4, CSMD1, TNR, KMT2C, NF1, RP1L1.

If you'd like this expanded to include amplifications/deletions/fusions, or run in a different lung adenocarcinoma cohort (e.g., MSK-IMPACT), let me know.