Q (sonnet): are lung carcinosarcomas associated with BRIP1 mutations?

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

▶ search_oncotree
{
 "search_term": "carcinosarcoma lung"
}

◀ 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)

◀ result
{"result":[]}

▶ search_oncotree
{
 "search_term": "carcinosarcoma"
}

▶ list_studies
{
 "search": "lung",
 "limit": 30
}

◀ result
{"result":[{"code":"CSNOS","name":"Breast Invasive Carcinosarcoma, NOS","score":50,"mainType":"Breast Cancer","tissue":"Breast","hierarchy":"BREAST > BRCA > CSNOS"},{"code":"MCS","name":"Metaplastic Carcinosarcoma","score":50,"mainType":"Breast Cancer","tissue":"Breast","hierarchy":"BREAST > MBC > MMBC > MCS"},{"code":"OCS","name":"Ovarian Carcinosarcoma/Malignant Mixed Mesodermal Tumor","score":50,"mainType":"Ovarian Cancer","tissue":"Ovary/Fallopian Tube","hierarchy":"OVARY > OVT > OCS"},{"code":"UCS","name":"Uterine Carcinosarcoma/Uterine Malignant Mixed Mullerian Tumor","score":50,"mainType":"Endometrial Cancer","tissue":"Uterus","hierarchy":"UTERUS > UCEC > UCS"}]}

◀ 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":"nsclc_ctdx_msk_2022","name":"Metastatic Non-Small Cell Lung Cancer (MSK, Nature Medicine 2022)","type_of_cancer_id":"nsclc","sample_count":2621,"has_guide":false,"url":"https://www.cbioportal.org/study/summary?id=nsclc_ctdx_msk_2022"},{"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":"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":"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":"nsclc_tracerx_2017","name":"Non-Small Cell Lung Cancer (TRACERx, NEJM & N … (4121 more chars)

▶ clickhouse_run_select_query
{
 "query": "SELECT DISTINCT attribute_value, cancer_study_identifier
FROM clinical_data_derived
WHERE attribute_name = 'CANCER_TYPE_DETAILED'
  AND lower(attribute_value) LIKE '%carcinosarcoma%'
ORDER BY cancer_study_identifier"
}

◀ result
{"rows":[{"attribute_value":"Breast Invasive Carcinosarcoma, NOS","cancer_study_identifier":"brca_msk_2025"},{"attribute_value":"Breast Invasive Carcinosarcoma, NOS","cancer_study_identifier":"breast_ink4_msk_2021"},{"attribute_value":"Breast Invasive Carcinosarcoma, NOS","cancer_study_identifier":"breast_msk_2025"},{"attribute_value":"Breast Invasive Carcinosarcoma, NOS","cancer_study_identifier":"breast_msk_2026"},{"attribute_value":"Metaplastic Carcinosarcoma","cancer_study_identifier":"breast_msk_2026"},{"attribute_value":"Uterine Carcinosarcoma/Uterine Malignant Mixed Mullerian Tumor","cancer_study_identifier":"ccle_broad_2019"},{"attribute_value":"Uterine Carcinosarcoma/Uterine Malignant Mixed Mullerian Tumor","cancer_study_identifier":"ccle_broad_2025"},{"attribute_value":"Ovarian Carcinosarcoma/Malignant Mixed Mesodermal Tumor","cancer_study_identifier":"cellline_ccle_broad"},{"attribute_value":"Breast Invasive Carcinosarcoma, NOS","cancer_study_identifier":"msk_chord_2024"},{"attribute_value":"Metaplastic Carcinosarcoma","cancer_study_identifier":"msk_chord_2024"},{"attribute_value":"Uterine Carcinosarcoma/Uterine Malignant Mixed Mullerian Tumor","cancer_study_identifier":"msk_ctdna_vte_2024"},{"attribute_value":"Uterine Carcinosarcoma/Uterine Malignant Mixed Mullerian Tumor","cancer_study_identifier":"msk_impact_2017"},{"attribute_value":"Ovarian Carcinosarcoma/Malignant Mixed Mesodermal Tumor","cancer_study_identifier":"msk_impact_2017"},{"attribute_value":"Ovarian Carcinosarcoma/Malignant Mixed Mesodermal Tumor","cancer_study_identifier":"msk_impact_50k_2026"},{"attribute_value":"Uterine Carcinosarcoma/Uterine Malignant Mixed Mullerian Tumor","cancer_study_identifier":"msk_impact_50k_2026"},{"attribute_value":"Breast Invasive Carcinosarcoma, NOS","cancer_study_identifier":"msk_impact_50k_2026"},{"attribute_value":"Metaplastic Carcinosarcoma","cancer_study_identifier":"msk_impact_50k_2026"},{"attribute_value":"Uterine Carcinosarcoma/Uterine Malignant Mixed Mullerian Tumor","cancer_study_identifier":"msk_met_2021"},{"attribute_value":"Uterine Carcinosarcoma/Uterine Malignant Mixed Mullerian Tumor","cancer_study_identifier":"mycf_msk_2026"},{"attribute_value":"Ovarian Carcinosarcoma/Malignant Mixed Mesodermal Tumor","cancer_study_identifier":"mycf_msk_2026"},{"attribute_value":"Metaplastic Carcinosarcoma","cancer_study_identifier":"pancan_hcmi_2025"},{"attribute_value":"Uterine Carcinosarcoma/Uterine Malignant Mixed Mullerian Tumor","cancer_study_identifier":"pancan_mimsi_msk_2024"},{"attribute_value":"Ovarian Carcinosarcoma/Malignant Mixed Mesodermal Tumor","cancer_study_identifier":"pancan_mimsi_msk_2024"},{"attribute_value":"Ovarian Carcinosarcoma/Malignant Mixed Mesodermal Tumor","cancer_study_identifier":"pancan_pdmr_2025"},{"attribute_value":"Uterine Carcinosarcoma/Uterine Malignant Mixed Mullerian Tumor","cancer_study_identifier":"pancan_pdmr_2025"},{"attribute_value":"Breast Invasive Carcinosarcoma, NOS","cancer_study_identifier" … (1185 more chars)

▶ clickhouse_run_select_query
{
 "query": "SELECT DISTINCT attribute_value, cancer_study_identifier
FROM clinical_data_derived
WHERE attribute_name IN ('CANCER_TYPE_DETAILED','CANCER_TYPE')
  AND (lower(attribute_value) LIKE '%sarcomatoid%' OR lower(attribute_value) LIKE '%pleomorphic%')
  AND lower(cancer_study_identifier) LIKE '%lung%' OR lower(attribute_value) LIKE '%lung%sarcomatoid%'
ORDER BY cancer_study_identifier"
}

◀ result
{"rows":[{"attribute_value":"Pleomorphic Carcinoma of the Lung","cancer_study_identifier":"lung_msk_mind_2020"},{"attribute_value":"Sarcomatoid Carcinoma of the Lung","cancer_study_identifier":"lung_msk_pdx"},{"attribute_value":"Pleomorphic Carcinoma of the Lung","cancer_study_identifier":"lung_msk_pdx"}]}

═ answer (success)
These are related pulmonary sarcomatoid entities but distinct from carcinosarcoma specifically, and cohorts are very small (PDX study). I won't substitute these for the user's actual question.

## Answer

**cBioPortal's database does not contain any lung carcinosarcoma cases**, so this association cannot be assessed with the data available here.

I checked both OncoTree (the cancer-type ontology cBioPortal uses) and every study's clinical annotations for the term "carcinosarcoma." Carcinosarcoma appears only as a recognized diagnosis for three primary sites:

- **Breast** invasive/metaplastic carcinosarcoma
- **Ovarian** carcinosarcoma (malignant mixed Müllerian tumor)
- **Uterine** carcinosarcoma (e.g., the TCGA [Uterine Carcinosarcoma (PanCancer Atlas)](https://www.cbioportal.org/study/summary?id=ucs_tcga_pan_can_atlas_2018) study)

There is no "Lung Carcinosarcoma" OncoTree code, and no lung cancer study in cBioPortal has any sample labeled with that diagnosis — including TCGA LUAD/LUSC, MSK-IMPACT, MSK-CHORD, TRACERx, or any other lung cohort.

I did find two related but distinct pulmonary entities in small MSK cohorts — "Sarcomatoid Carcinoma of the Lung" and "Pleomorphic Carcinoma of the Lung" (in `lung_msk_pdx`, a small PDX study, and `lung_msk_mind_2020`) — but these are separate diagnostic categories from carcinosarcoma, and I won't substitute them for your question without confirming that's what you meant.

**A note on scope:** Lung carcinosarcoma is a very rare tumor type, and it's plausible that published case reports or series describing BRIP1 mutations in it exist in the literature outside of cBioPortal. That would be a literature question rather than something this database can confirm — I have no data to support or refute a BRIP1 association in lung carcinosarcoma specifically.

If you'd like, I can instead:
1. Check BRIP1 mutation frequency in **uterine or ovarian carcinosarcoma** (where cBioPortal does have data), or
2. Check BRIP1 in the **sarcomatoid/pleomorphic lung carcinoma** cohorts noted above, or
3. Confirm you meant a different lung histology.

Let me know which direction is useful.