Q (sonnet-5.5): What are the key genomic differences between lung adenocarcinomas and squamous cell carcinomas identified in the Pan-Lung Cancer TCGA study?

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

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

◀ result
{"result":[{"cancer_study_identifier":"nsclc_tcga_broad_2016","name":"Pan-Lung Cancer (TCGA, Nat Genet 2016)","type_of_cancer_id":"nsclc","sample_count":1144,"has_guide":false,"url":"https://www.cbioportal.org/study/summary?id=nsclc_tcga_broad_2016"},{"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":"lusc_tcga","name":"Lung Squamous Cell Carcinoma (TCGA, Firehose Legacy)","type_of_cancer_id":"lusc","sample_count":511,"has_guide":false,"url":"https://www.cbioportal.org/study/summary?id=lusc_tcga"},{"cancer_study_identifier":"lusc_tcga_gdc","name":"Lung Squamous Cell Carcinoma (TCGA GDC, 2025)","type_of_cancer_id":"lusc","sample_count":503,"has_guide":false,"url":"https://www.cbioportal.org/study/summary?id=lusc_tcga_gdc"},{"cancer_study_identifier":"lusc_tcga_pan_can_atlas_2018","name":"Lung Squamous Cell Carcinoma (TCGA, PanCancer Atlas)","type_of_cancer_id":"lusc","sample_count":487,"has_guide":false,"url":"https://www.cbioportal.org/study/summary?id=lusc_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"},{"cancer_study_identifier":"lusc_tcga_pub","name":"Lung Squamous Cell Carcinoma (TCGA, Nature 2012)","type_of_cancer_id":"lusc","sample_count":178,"has_guide":false,"url":"https://www.cbioportal.org/study/summary?id=lusc_tcga_pub"}]}

◀ 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)

▶ clickhouse_run_select_query
{
 "query": "SELECT attribute_name, attribute_value, count() c FROM clinical_data_derived WHERE cancer_study_identifier='nsclc_tcga_broad_2016' AND attribute_name IN ('CANCER_TYPE_DETAILED','HISTOLOGICAL_SUBTYPE','CANCER_TYPE') GROUP BY 1,2 ORDER BY 1,3 DESC"
}

▶ clickhouse_run_select_query
{
 "query": "SELECT DISTINCT genetic_profile_id, genetic_alteration_type, datatype FROM genetic_profile WHERE cancer_study_identifier='nsclc_tcga_broad_2016'"
}

◀ result
{"rows":[{"attribute_name":"CANCER_TYPE","attribute_value":"Non-Small Cell Lung Cancer","c":1144},{"attribute_name":"CANCER_TYPE_DETAILED","attribute_value":"Lung Adenocarcinoma","c":660},{"attribute_name":"CANCER_TYPE_DETAILED","attribute_value":"Lung Squamous Cell Carcinoma","c":484}]}

◀ 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 or function identifier `cancer_study_identifier` in scope SELECT DISTINCT genetic_profile_id, genetic_alteration_type, datatype FROM genetic_profile WHERE cancer_study_identifier = 'nsclc_tcga_broad_2016'. (UNKNOWN_IDENTIFIER) (version 26.4.1.2509 (official build))\n"}

▶ clickhouse_run_select_query
{
 "query": "WITH st AS (SELECT sample_unique_id, attribute_value AS sub FROM clinical_data_derived WHERE cancer_study_identifier='nsclc_tcga_broad_2016' AND attribute_name='CANCER_TYPE_DETAILED'),
prof AS (SELECT sample_unique_id FROM sample_to_gene_panel_derived WHERE cancer_study_identifier='nsclc_tcga_broad_2016' AND alteration_type='MUTATION_EXTENDED'),
den AS (SELECT sub, count() n FROM st WHERE sample_unique_id IN (SELECT sample_unique_id FROM prof) GROUP BY sub),
alt AS (SELECT st.sub sub, g.hugo_gene_symbol gene, uniqExact(g.sample_unique_id) a FROM genomic_event_derived g JOIN st USING sample_unique_id WHERE g.cancer_study_identifier='nsclc_tcga_broad_2016' AND g.variant_type='mutation' AND g.mutation_status!='UNCALLED' AND g.hugo_gene_symbol IN ('TP53','KRAS','EGFR','BRAF','STK11','KEAP1','NF1','RBM10','MET','ERBB2','U2AF1','SMARCA4','RB1','CDKN2A','PIK3CA','PTEN','NFE2L2','KMT2D','FAT1','ARID1A','NOTCH1','HRAS','SETD2','MGA','TTN','MUC16') GROUP BY sub, gene)
SELECT gene, sumIf(a, sub='Lung Adenocarcinoma') luad_n, anyIf(n, sub='Lung Adenocarcinoma') luad_prof, round(luad_n*100/luad_prof,1) luad_pct, sumIf(a, sub='Lung Squamous Cell Carcinoma') lusc_n, anyIf(n, sub='Lung Squamous Cell Carcinoma') lusc_prof, round(lusc_n*100/lusc_prof,1) lusc_pct FROM alt JOIN den USING sub GROUP BY gene ORDER BY luad_pct DESC"
}

◀ result
{"rows":[{"gene":"TP53","luad_n":357,"luad_prof":660,"luad_pct":54.1,"lusc_n":418,"lusc_prof":484,"lusc_pct":86.4},{"gene":"TTN","luad_n":325,"luad_prof":660,"luad_pct":49.2,"lusc_n":357,"lusc_prof":484,"lusc_pct":73.8},{"gene":"MUC16","luad_n":271,"luad_prof":660,"luad_pct":41.1,"lusc_n":192,"lusc_prof":484,"lusc_pct":39.7},{"gene":"KRAS","luad_n":214,"luad_prof":660,"luad_pct":32.4,"lusc_n":8,"lusc_prof":484,"lusc_pct":1.7},{"gene":"KEAP1","luad_n":110,"luad_prof":660,"luad_pct":16.7,"lusc_n":52,"lusc_prof":484,"lusc_pct":10.7},{"gene":"EGFR","luad_n":104,"luad_prof":660,"luad_pct":15.8,"lusc_n":13,"lusc_prof":484,"lusc_pct":2.7},{"gene":"STK11","luad_n":104,"luad_prof":660,"luad_pct":15.8,"lusc_n":7,"lusc_prof":484,"lusc_pct":1.4},{"gene":"NF1","luad_n":76,"luad_prof":660,"luad_pct":11.5,"lusc_n":51,"lusc_prof":484,"lusc_pct":10.5},{"gene":"FAT1","luad_n":73,"luad_prof":660,"luad_pct":11.1,"lusc_n":69,"lusc_prof":484,"lusc_pct":14.3},{"gene":"SMARCA4","luad_n":61,"luad_prof":660,"luad_pct":9.2,"lusc_n":18,"lusc_prof":484,"lusc_pct":3.7},{"gene":"BRAF","luad_n":54,"luad_prof":660,"luad_pct":8.2,"lusc_n":16,"lusc_prof":484,"lusc_pct":3.3},{"gene":"KMT2D","luad_n":49,"luad_prof":660,"luad_pct":7.4,"lusc_n":114,"lusc_prof":484,"lusc_pct":23.6},{"gene":"ARID1A","luad_n":48,"luad_prof":660,"luad_pct":7.3,"lusc_n":32,"lusc_prof":484,"lusc_pct":6.6},{"gene":"MGA","luad_n":42,"luad_prof":660,"luad_pct":6.4,"lusc_n":17,"lusc_prof":484,"lusc_pct":3.5},{"gene":"RBM10","luad_n":41,"luad_prof":660,"luad_pct":6.2,"lusc_n":6,"lusc_prof":484,"lusc_pct":1.2},{"gene":"PIK3CA","luad_n":39,"luad_prof":660,"luad_pct":5.9,"lusc_n":55,"lusc_prof":484,"lusc_pct":11.4},{"gene":"SETD2","luad_n":38,"luad_prof":660,"luad_pct":5.8,"lusc_n":14,"lusc_prof":484,"lusc_pct":2.9},{"gene":"RB1","luad_n":38,"luad_prof":660,"luad_pct":5.8,"lusc_n":35,"lusc_prof":484,"lusc_pct":7.2},{"gene":"NOTCH1","luad_n":31,"luad_prof":660,"luad_pct":4.7,"lusc_n":40,"lusc_prof":484,"lusc_pct":8.3},{"gene":"MET","luad_n":28,"luad_prof":660,"luad_pct":4.2,"lusc_n":6,"lusc_prof":484,"lusc_pct":1.2},{"gene":"CDKN2A","luad_n":27,"luad_prof":660,"luad_pct":4.1,"lusc_n":75,"lusc_prof":484,"lusc_pct":15.5},{"gene":"U2AF1","luad_n":17,"luad_prof":660,"luad_pct":2.6,"lusc_n":0,"lusc_prof":0,"lusc_pct":null},{"gene":"ERBB2","luad_n":17,"luad_prof":660,"luad_pct":2.6,"lusc_n":9,"lusc_prof":484,"lusc_pct":1.9},{"gene":"NFE2L2","luad_n":14,"luad_prof":660,"luad_pct":2.1,"lusc_n":70,"lusc_prof":484,"lusc_pct":14.5},{"gene":"PTEN","luad_n":11,"luad_prof":660,"luad_pct":1.7,"lusc_n":56,"lusc_prof":484,"lusc_pct":11.6},{"gene":"HRAS","luad_n":3,"luad_prof":660,"luad_pct":0.5,"lusc_n":8,"lusc_prof":484,"lusc_pct":1.7}]}

▶ clickhouse_run_select_query
{
 "query": "WITH st AS (SELECT sample_unique_id, attribute_value AS sub FROM clinical_data_derived WHERE cancer_study_identifier='nsclc_tcga_broad_2016' AND attribute_name='CANCER_TYPE_DETAILED'),
prof AS (SELECT sample_unique_id FROM sample_to_gene_panel_derived WHERE cancer_study_identifier='nsclc_tcga_broad_2016' AND alteration_type='COPY_NUMBER_ALTERATION'),
den AS (SELECT sub, count() n FROM st WHERE sample_unique_id IN (SELECT sample_unique_id FROM prof) GROUP BY sub),
alt AS (SELECT st.sub sub, g.hugo_gene_symbol gene, g.cna_alteration t, uniqExact(g.sample_unique_id) a FROM genomic_event_derived g JOIN st USING sample_unique_id WHERE g.cancer_study_identifier='nsclc_tcga_broad_2016' AND g.variant_type='cna' AND g.hugo_gene_symbol IN ('SOX2','TP63','PIK3CA','NKX2-1','CDKN2A','EGFR','MYC','KRAS','FGFR1','PTEN','MDM2','CCND1','ERBB2','MET','TERT','NFE2L2','RB1','STK11') GROUP BY sub, gene, t)
SELECT gene, t, sumIf(a, sub='Lung Adenocarcinoma') luad_n, anyIf(n, sub='Lung Adenocarcinoma') luad_prof, round(luad_n*100/luad_prof,1) luad_pct, sumIf(a, sub='Lung Squamous Cell Carcinoma') lusc_n, anyIf(n, sub='Lung Squamous Cell Carcinoma') lusc_prof, round(lusc_n*100/lusc_prof,1) lusc_pct FROM alt JOIN den USING sub GROUP BY gene, t HAVING luad_n+lusc_n>=10 ORDER BY gene"
}

◀ result
{"rows":[{"gene":"CCND1","t":2,"luad_n":26,"luad_prof":660,"luad_pct":3.9,"lusc_n":63,"lusc_prof":484,"lusc_pct":13},{"gene":"CDKN2A","t":-2,"luad_n":112,"luad_prof":660,"luad_pct":17,"lusc_n":129,"lusc_prof":484,"lusc_pct":26.7},{"gene":"EGFR","t":2,"luad_n":36,"luad_prof":660,"luad_pct":5.5,"lusc_n":33,"lusc_prof":484,"lusc_pct":6.8},{"gene":"ERBB2","t":2,"luad_n":15,"luad_prof":660,"luad_pct":2.3,"lusc_n":11,"lusc_prof":484,"lusc_pct":2.3},{"gene":"FGFR1","t":-2,"luad_n":10,"luad_prof":660,"luad_pct":1.5,"lusc_n":2,"lusc_prof":484,"lusc_pct":0.4},{"gene":"FGFR1","t":2,"luad_n":19,"luad_prof":660,"luad_pct":2.9,"lusc_n":83,"lusc_prof":484,"lusc_pct":17.1},{"gene":"KRAS","t":2,"luad_n":40,"luad_prof":660,"luad_pct":6.1,"lusc_n":18,"lusc_prof":484,"lusc_pct":3.7},{"gene":"MDM2","t":2,"luad_n":36,"luad_prof":660,"luad_pct":5.5,"lusc_n":10,"lusc_prof":484,"lusc_pct":2.1},{"gene":"MET","t":2,"luad_n":14,"luad_prof":660,"luad_pct":2.1,"lusc_n":5,"lusc_prof":484,"lusc_pct":1},{"gene":"MYC","t":2,"luad_n":62,"luad_prof":660,"luad_pct":9.4,"lusc_n":38,"lusc_prof":484,"lusc_pct":7.9},{"gene":"NFE2L2","t":2,"luad_n":6,"luad_prof":660,"luad_pct":0.9,"lusc_n":19,"lusc_prof":484,"lusc_pct":3.9},{"gene":"NKX2-1","t":2,"luad_n":79,"luad_prof":660,"luad_pct":12,"lusc_n":13,"lusc_prof":484,"lusc_pct":2.7},{"gene":"PIK3CA","t":2,"luad_n":14,"luad_prof":660,"luad_pct":2.1,"lusc_n":194,"lusc_prof":484,"lusc_pct":40.1},{"gene":"PTEN","t":-2,"luad_n":5,"luad_prof":660,"luad_pct":0.8,"lusc_n":31,"lusc_prof":484,"lusc_pct":6.4},{"gene":"RB1","t":-2,"luad_n":7,"luad_prof":660,"luad_pct":1.1,"lusc_n":10,"lusc_prof":484,"lusc_pct":2.1},{"gene":"SOX2","t":2,"luad_n":15,"luad_prof":660,"luad_pct":2.3,"lusc_n":205,"lusc_prof":484,"lusc_pct":42.4},{"gene":"TERT","t":2,"luad_n":98,"luad_prof":660,"luad_pct":14.8,"lusc_n":73,"lusc_prof":484,"lusc_pct":15.1},{"gene":"TP63","t":2,"luad_n":13,"luad_prof":660,"luad_pct":2,"lusc_n":163,"lusc_prof":484,"lusc_pct":33.7}]}

▶ resolve_and_route
{
 "studyIds": [
  "nsclc_tcga_broad_2016"
 ]
}

◀ result
{"success":true,"message":"Found 1 study. Use the metadata to call the appropriate navigation tool(s).","data":{"totalCount":1,"studiesWithMetadata":[{"studyId":"nsclc_tcga_broad_2016","name":"Pan-Lung Cancer (TCGA, Nat Genet 2016)","sampleCount":1144,"studyViewUrl":"https://www.cbioportal.org/study?id=nsclc_tcga_broad_2016","metadata":{"clinicalAttributeIds":["AGE","AGE_AT_SURGERY","CANCER_TYPE","CANCER_TYPE_DETAILED","DAYS_TO_DEATH","DAYS_TO_LAST_FOLLOWUP","FRACTION_GENOME_ALTERED","HISTORY_NEOADJUVANT_TRTYN","HISTORY_OTHER_MALIGNANCY","MUTATION_COUNT","M_STAGE","N_STAGE","ONCOTREE_CODE","OS_MONTHS","OS_STATUS","SAMPLE_COUNT","SEX","SMOKING_HISTORY","SMOKING_PACK_YEARS","SOMATIC_STATUS","STAGE","TMB_NONSYNONYMOUS","T_STAGE"],"molecularProfileIds":["nsclc_tcga_broad_2016_cna","nsclc_tcga_broad_2016_mutations","nsclc_tcga_broad_2016_structural_variants"],"availableComparisonTabs":["overlap","clinical","survival","alterations","mutations"]}}]}}

▶ get_studyviewfilter_options
{
 "studyId": "nsclc_tcga_broad_2016",
 "attributeIds": [
  "CANCER_TYPE_DETAILED"
 ]
}

◀ result
{"success":true,"message":"Successfully retrieved StudyView filter options","data":{"studyId":"nsclc_tcga_broad_2016","attributes":[{"attributeId":"CANCER_TYPE_DETAILED","displayName":"Cancer Type Detailed","description":"Cancer Type Detailed","datatype":"STRING","values":["Lung Adenocarcinoma","Lung Squamous Cell Carcinoma"]}]}}

▶ navigate_to_group_comparison
{
 "studyIds": [
  "nsclc_tcga_broad_2016"
 ],
 "groups": [
  {
   "name": "Lung Adenocarcinoma",
   "studyViewFilter": {
    "clinicalDataFilters": [
     {
      "attributeId": "CANCER_TYPE_DETAILED",
      "values": [
       {
        "value": "Lung Adenocarcinoma"
       }
      ]
     }
    ]
   }
  },
  {
   "name": "Lung Squamous Cell Carcinoma",
   "studyViewFilter": {
    "clinicalDataFilters": [
     {
      "attributeId": "CANCER_TYPE_DETAILED",
      "values": [
       {
        "value": "Lung Squamous Cell Carcinoma"
       }
      ]
     }
    ]
   }
  }
 ],
 "tab": "alterations"
}

◀ result
{"success":true,"message":"Navigating to https://www.cbioportal.org/comparison/alterations?comparisonId=6ab4329ee497aad53593be0b","url":"https://www.cbioportal.org/comparison/alterations?comparisonId=6ab4329ee497aad53593be0b","data":{"description":"Group comparison (2 custom groups)","studies":["nsclc_tcga_broad_2016"],"totalGroups":2,"groups":[{"name":"Lung Adenocarcinoma","sampleCount":660},{"name":"Lung Squamous Cell Carcinoma","sampleCount":484}],"studyViewUrl":"https://www.cbioportal.org/study?id=nsclc_tcga_broad_2016","groupUrls":[{"groupName":"Lung Adenocarcinoma","url":"https://www.cbioportal.org/study?id=nsclc_tcga_broad_2016#filterJson=%7B%22clinicalDataFilters%22%3A%5B%7B%22attributeId%22%3A%22CANCER_TYPE_DETAILED%22%2C%22values%22%3A%5B%7B%22value%22%3A%22Lung%20Adenocarcinoma%22%7D%5D%7D%5D%7D"},{"groupName":"Lung Squamous Cell Carcinoma","url":"https://www.cbioportal.org/study?id=nsclc_tcga_broad_2016#filterJson=%7B%22clinicalDataFilters%22%3A%5B%7B%22attributeId%22%3A%22CANCER_TYPE_DETAILED%22%2C%22values%22%3A%5B%7B%22value%22%3A%22Lung%20Squamous%20Cell%20Carcinoma%22%7D%5D%7D%5D%7D"}],"pageDescription":"Comparison of genomic alteration rates across Lung Adenocarcinoma (660) vs Lung Squamous Cell Carcinoma (484)."}}

═ answer (success)
I compared lung adenocarcinoma (LUAD) with lung squamous cell carcinoma (LUSC) in [Pan-Lung Cancer (TCGA, Nat Genet 2016)](https://www.cbioportal.org/study/summary?id=nsclc_tcga_broad_2016). The study has 660 LUAD and 484 LUSC samples, and the counts below are per sample. I haven't run significance tests. The percentages are descriptive, and the Group Comparison link below runs the enrichment statistics.

## Mutations (altered / profiled samples)

| Gene | LUAD | LUSC | Pattern |
|---|---|---|---|
| KRAS | 214/660 (32.4%) | 8/484 (1.7%) | LUAD |
| EGFR | 104/660 (15.8%) | 13/484 (2.7%) | LUAD |
| STK11 | 104/660 (15.8%) | 7/484 (1.4%) | LUAD |
| BRAF | 54/660 (8.2%) | 16/484 (3.3%) | LUAD |
| RBM10 | 41/660 (6.2%) | 6/484 (1.2%) | LUAD |
| SMARCA4 | 61/660 (9.2%) | 18/484 (3.7%) | LUAD |
| U2AF1 | 17/660 (2.6%) | 0/484 (0%) | LUAD only |
| KEAP1 | 110/660 (16.7%) | 52/484 (10.7%) | Higher in LUAD |
| TP53 | 357/660 (54.1%) | 418/484 (86.4%) | LUSC |
| KMT2D | 49/660 (7.4%) | 114/484 (23.6%) | LUSC |
| CDKN2A | 27/660 (4.1%) | 75/484 (15.5%) | LUSC |
| NFE2L2 | 14/660 (2.1%) | 70/484 (14.5%) | LUSC |
| PTEN | 11/660 (1.7%) | 56/484 (11.6%) | LUSC |
| PIK3CA | 39/660 (5.9%) | 55/484 (11.4%) | Higher in LUSC |
| NOTCH1 | 31/660 (4.7%) | 40/484 (8.3%) | Higher in LUSC |

NF1 (11.5% vs 10.5%), FAT1 (11.1% vs 14.3%) and MUC16 (41.1% vs 39.7%) are similar in the two subtypes. TTN is more frequent in LUSC (49.2% vs 73.8%), but it is a very large gene and often a passenger, so I wouldn't read much into it.

## Copy-number changes (amplification unless noted)

| Gene | LUAD | LUSC | Pattern |
|---|---|---|---|
| NKX2-1 (amplification) | 79/660 (12.0%) | 13/484 (2.7%) | LUAD |
| MDM2 (amplification) | 36/660 (5.5%) | 10/484 (2.1%) | Higher in LUAD |
| SOX2 (amplification) | 15/660 (2.3%) | 205/484 (42.4%) | LUSC |
| TP63 (amplification) | 13/660 (2.0%) | 163/484 (33.7%) | LUSC |
| PIK3CA (amplification) | 14/660 (2.1%) | 194/484 (40.1%) | LUSC |
| FGFR1 (amplification) | 19/660 (2.9%) | 83/484 (17.1%) | LUSC |
| CCND1 (amplification) | 26/660 (3.9%) | 63/484 (13.0%) | LUSC |
| CDKN2A (homozygous deletion) | 112/660 (17.0%) | 129/484 (26.7%) | Higher in LUSC |
| PTEN (homozygous deletion) | 5/660 (0.8%) | 31/484 (6.4%) | LUSC |

TERT amplification (about 15% in both subtypes) and MYC amplification (9.4% vs 7.9%) are shared.

## Summary
- **LUAD** is characterized by mutations in the RTK/RAS/RAF pathway (KRAS, EGFR, BRAF), along with STK11, RBM10 and U2AF1. It also shows NKX2-1 (TTF-1) amplification.
- **LUSC** is characterized by very frequent TP53 mutation and by loss of CDKN2A, PTEN and KMT2D. NFE2L2 is mutated in about 15% of LUSC. Amplification of the 3q26 and 8p11 regions is common. That includes SOX2, TP63 and PIK3CA on 3q, and FGFR1 on 8p. Together with mutations, this points to PI3K pathway and squamous-lineage activation.

This summary is based only on the cBioPortal counts above. It does not draw on the published paper.

[Open the LUAD vs LUSC alteration enrichment comparison](https://www.cbioportal.org/comparison/alterations?comparisonId=6ab4329ee497aad53593be0b) (660 vs 484 samples) for per-gene statistics. You can also [browse the whole cohort in Study View](https://www.cbioportal.org/study?id=nsclc_tcga_broad_2016).