Q (haiku):
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?
▶ read_guide
{
"uri": "cbioportal://mutation-frequency-guide"
}
▶ list_studies
{
"search": "TCGA lung squamous"
}
◀ 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)
✗ error
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▶ list_studies
{
"search": "TCGA squamous"
}
◀ result
{"result":[{"cancer_study_identifier":"hnsc_tcga_gdc","name":"Head and Neck Squamous Cell Carcinoma (TCGA GDC, 2025)","type_of_cancer_id":"hnsc","sample_count":530,"has_guide":false,"url":"https://www.cbioportal.org/study/summary?id=hnsc_tcga_gdc"},{"cancer_study_identifier":"hnsc_tcga","name":"Head and Neck Squamous Cell Carcinoma (TCGA, Firehose Legacy)","type_of_cancer_id":"hnsc","sample_count":530,"has_guide":false,"url":"https://www.cbioportal.org/study/summary?id=hnsc_tcga"},{"cancer_study_identifier":"hnsc_tcga_pan_can_atlas_2018","name":"Head and Neck Squamous Cell Carcinoma (TCGA, PanCancer Atlas)","type_of_cancer_id":"hnsc","sample_count":523,"has_guide":false,"url":"https://www.cbioportal.org/study/summary?id=hnsc_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":"cesc_tcga","name":"Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (TCGA, Firehose Legacy)","type_of_cancer_id":"cesc","sample_count":310,"has_guide":false,"url":"https://www.cbioportal.org/study/summary?id=cesc_tcga"},{"cancer_study_identifier":"cesc_tcga_gdc","name":"Cervical Squamous Cell Carcinoma (TCGA GDC, 2025)","type_of_cancer_id":"cesc","sample_count":309,"has_guide":false,"url":"https://www.cbioportal.org/study/summary?id=cesc_tcga_gdc"},{"cancer_study_identifier":"cesc_tcga_pan_can_atlas_2018","name":"Cervical Squamous Cell Carcinoma (TCGA, PanCancer Atlas)","type_of_cancer_id":"cesc","sample_count":297,"has_guide":false,"url":"https://www.cbioportal.org/study/summary?id=cesc_tcga_pan_can_atlas_2018"},{"cancer_study_identifier":"hnsc_tcga_pub","name":"Head and Neck Squamous Cell Carcinoma (TCGA, Nature 2015)","type_of_cancer_id":"hnsc","sample_count":279,"has_guide":false,"url":"https://www.cbioportal.org/study/summary?id=hnsc_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"}]}
▶ clickhouse_run_select_query
{
"query": "
SELECT *
FROM gene_mutation_variants_in_study(
study = 'lusc_tcga_pan_can_atlas_2018',
gene = 'KRAS'
)
ORDER BY frequency_pct DESC
"
}
◀ 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}]}
▶ clickhouse_run_select_query
{
"query": "
SELECT *
FROM gene_mutation_frequency_in_study(
study = 'lusc_tcga_pan_can_atlas_2018',
gene = 'KRAS'
)
"
}
◀ result
{"rows":[{"cancer_type":"Non-Small Cell Lung Cancer","altered_samples":7,"profiled_samples":484,"frequency_pct":1.4}]}
═ answer (success)
In **Lung Squamous Cell Carcinoma (TCGA, PanCancer Atlas)**, KRAS mutations are very rare:
- **7 of 484 profiled samples (1.4%)** carry a KRAS mutation
This is a stark contrast to lung adenocarcinoma (29.7%). The variants are scattered:
- G12A: 1 (0.2%)
- G12V: 1 (0.2%)
- G13C: 1 (0.2%)
- Q61H: 1 (0.2%)
- V14I: 1 (0.2%)
- E3K: 1 (0.2%)
- R123*: 1 (0.2%)
**Key observation:** Squamous cell carcinomas (both lung and head-and-neck) have low KRAS mutation rates, while adenocarcinomas have high rates. This reflects a well-known histologic difference in lung cancer biology.