Q (sonnet):
What are the most common KRAS mutations in TCGA lung adenocarcinoma?
In Lung Adenocarcinoma (TCGA, PanCancer Atlas), 168 of 566 profiled samples (29.7%) have a KRAS mutation. The most common:
- G12C: 70 (12.4%)
- G12V: 40 (7.1%)
- G12D: 20 (3.5%)
- G12A: 17 (3.0%)
Continue this conversation: reply to the user's new message.
And in lung squamous?
▶ clickhouse_run_select_query
{
"query": "SELECT * FROM gene_mutation_variants_in_study WHERE cancer_study_identifier = 'lusc_tcga_pan_can_atlas_2018' AND hugo_gene_symbol = 'KRAS' ORDER BY variant_count DESC LIMIT 10"
}
◀ result
{"error_message":"Query execution failed: HTTPDriver for https://dl96orhu96.us-east-1.aws.clickhouse.cloud:8443 received ClickHouse error code 51\n Code: 51. DB::Exception: Empty list of columns in projection. In scope SELECT * FROM gene_mutation_variants_in_study WHERE (cancer_study_identifier = 'lusc_tcga_pan_can_atlas_2018') AND (hugo_gene_symbol = 'KRAS') ORDER BY variant_count DESC LIMIT 10. (EMPTY_LIST_OF_COLUMNS_QUERIED) (version 26.4.1.2359 (official build))\n"}
▶ clickhouse_run_select_query
{
"query": "SELECT * FROM gene_mutation_frequency_in_study WHERE cancer_study_identifier = 'lusc_tcga_pan_can_can_atlas_2018' AND hugo_gene_symbol = 'KRAS'"
}
◀ result
{"error_message":"Query execution failed: HTTPDriver for https://dl96orhu96.us-east-1.aws.clickhouse.cloud:8443 received ClickHouse error code 51\n Code: 51. DB::Exception: Empty list of columns in projection. In scope SELECT * FROM gene_mutation_frequency_in_study WHERE (cancer_study_identifier = 'lusc_tcga_pan_can_can_atlas_2018') AND (hugo_gene_symbol = 'KRAS'). (EMPTY_LIST_OF_COLUMNS_QUERIED) (version 26.4.1.2359 (official build))\n"}
▶ clickhouse_list_table_columns
{
"table": "gene_mutation_variants_in_study"
}
◀ result
{"columns":[]}
▶ clickhouse_list_table_columns
{
"table": "gene_mutation_frequency_in_study"
}
▶ list_studies
{
"search": "lung squamous"
}
◀ result
{"columns":[]}
◀ result
{"result":[{"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":"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"},{"cancer_study_identifier":"lusc_cptac_gdc","name":"Lung Squamous Cell Carcinoma (CPTAC GDC, 2025)","type_of_cancer_id":"lusc","sample_count":110,"has_guide":false,"url":"https://www.cbioportal.org/study/summary?id=lusc_cptac_gdc"},{"cancer_study_identifier":"lusc_cptac_2021","name":"Lung Squamous Cell Carcinoma (CPTAC, Cell 2021)","type_of_cancer_id":"lusc","sample_count":80,"has_guide":false,"url":"https://www.cbioportal.org/study/summary?id=lusc_cptac_2021"}]}
▶ read_guide
{
"uri": "cbioportal://mutation-frequency-guide"
}
◀ 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 * FROM gene_mutation_variants_in_study(study = 'lusc_tcga_pan_can_atlas_2018', gene = 'KRAS') ORDER BY altered_samples DESC LIMIT 10"
}
◀ result
{"rows":[{"mutation_variant":"G13C","mutation_type":"Missense_Mutation","altered_samples":1,"profiled_samples":484,"frequency_pct":0.2,"total_mutation_events":1},{"mutation_variant":"G12V","mutation_type":"Missense_Mutation","altered_samples":1,"profiled_samples":484,"frequency_pct":0.2,"total_mutation_events":1},{"mutation_variant":"E3K","mutation_type":"Missense_Mutation","altered_samples":1,"profiled_samples":484,"frequency_pct":0.2,"total_mutation_events":1},{"mutation_variant":"R123*","mutation_type":"Nonsense_Mutation","altered_samples":1,"profiled_samples":484,"frequency_pct":0.2,"total_mutation_events":1},{"mutation_variant":"Q61H","mutation_type":"Missense_Mutation","altered_samples":1,"profiled_samples":484,"frequency_pct":0.2,"total_mutation_events":1},{"mutation_variant":"V14I","mutation_type":"Missense_Mutation","altered_samples":1,"profiled_samples":484,"frequency_pct":0.2,"total_mutation_events":1},{"mutation_variant":"G12A","mutation_type":"Missense_Mutation","altered_samples":1,"profiled_samples":484,"frequency_pct":0.2,"total_mutation_events":1}]}
▶ resolve_and_route
{
"studyIds": [
"lusc_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":"lusc_tcga_pan_can_atlas_2018","name":"Lung Squamous Cell Carcinoma (TCGA, PanCancer Atlas)","sampleCount":487,"studyViewUrl":"https://www.cbioportal.org/study?id=lusc_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":["lusc_tcga_pan_can_atlas_2018_gistic","lusc_tcga_pan_can_atlas_2018_log2CNA","lusc_tcga_pan_can_atlas_2018_mutations","lusc_tcga_pan_can_atlas_2018_rna_seq_v2_mrna","lusc_tcga_pan_can_atlas_2018_rna_seq_v2_mrna_median_Zscores","lusc_tcga_pan_can_atlas_2018_rna_seq_v2_mrna_median_all_sample_Zscores","lusc_tcga_pan_can_atlas_2018_rna_seq_v2_mrna_median_all_sample_ref_normal_Zscores","lusc_tcga_pan_can_atlas_2018_rppa","lusc_tcga_pan_can_atlas_2018_rppa_Zscores","lusc_tcga_pan_can_atlas_2018_structural_variants"],"genericAssayProfiles":["lusc_tcga_pan_can_atlas_2018_armlevel_cna","lusc_tcga_pan_can_atlas_2018_genetic_ancestry","lusc_tcga_pan_can_atlas_2018_methylation_hm27_hm450_merge","lusc_tcga_pan_can_atlas_2018_methylation_hm450"],"heatmapProfileIds":["lusc_tcga_pan_can_atlas_2018_rna_seq_v2_mrna_median_Zscores","lusc_tcga_pan_can_atlas_2018_rna_seq_v2_mrna_median_all_sample_Zscores","lusc_tcga_pan_can_atlas_2018_rna_seq_v2_mrna_median_all_sample_ref_normal_Zscores","lusc_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"]}}]}}
▶ navigate_to_results_view
{
"studyIds": [
"lusc_tcga_pan_can_atlas_2018"
],
"genes": [
"KRAS"
],
"tab": "mutations"
}
◀ result
{"success":true,"message":"Navigating to https://www.cbioportal.org/results/mutations?cancer_study_list=lusc_tcga_pan_can_atlas_2018&gene_list=KRAS&case_set_id=lusc_tcga_pan_can_atlas_2018_all","url":"https://www.cbioportal.org/results/mutations?cancer_study_list=lusc_tcga_pan_can_atlas_2018&gene_list=KRAS&case_set_id=lusc_tcga_pan_can_atlas_2018_all","data":{"studyIds":["lusc_tcga_pan_can_atlas_2018"],"studies":[{"studyId":"lusc_tcga_pan_can_atlas_2018","name":"Lung Squamous Cell Carcinoma (TCGA, PanCancer Atlas)","sampleCount":487}],"genes":["KRAS"],"caseSetId":"lusc_tcga_pan_can_atlas_2018_all","pageDescription":"Detailed mutation table with lollipop plot showing mutation positions, types, and frequencies for queried genes."}}
═ answer (success)
In Lung Squamous Cell Carcinoma (TCGA, PanCancer Atlas), KRAS mutations are rare — 7 of 484 profiled samples (1.4%), each a distinct variant occurring only once: G13C, G12V, E3K, R123*, Q61H, V14I, and G12A.
This is a sharp contrast to lung adenocarcinoma, where 29.7% of samples are KRAS-mutant with recurrent hotspots (G12C, G12V, G12D). KRAS mutation is a well-known histology-distinguishing feature between the two lung cancer subtypes.
[View KRAS mutations in Lung Squamous Cell Carcinoma (Mutations Tab)](https://www.cbioportal.org/results/mutations?cancer_study_list=lusc_tcga_pan_can_atlas_2018&gene_list=KRAS&case_set_id=lusc_tcga_pan_can_atlas_2018_all)