Q (haiku): show me cholangio with idh1 mutations other than r132 ▶ read_guide { "uri": "cbioportal://mutation-frequency-guide" } ▶ read_guide { "uri": "cbioportal://common-pitfalls" } ◀ 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) ▶ search_oncotree { "search_term": "cholangiocarcinoma" } ◀ result # Common Query Pitfalls Guide ## Overview This guide highlights frequent mistakes when analyzing cBioPortal data and provides solutions to avoid them. ## Critical Pitfalls ### 1. 🚨 CRITICAL MUTATION FREQUENCY ERRORS #### ❌ WRONG: Using study-wide totals for gene frequencies ```sql -- INCORRECT - This gives wrong frequencies! SELECT hugo_gene_symbol, COUNT(DISTINCT sample_unique_id) as altered_samples, (SELECT COUNT(DISTINCT sample_unique_id) FROM genomic_event_derived WHERE cancer_study_identifier = 'your_study_id') as total_samples FROM genomic_event_derived WHERE variant_type = 'mutation' AND cancer_study_identifier = 'your_study_id' GROUP BY hugo_gene_symbol; ``` **Problem**: Different genes have different profiling coverage - you can't use study-wide totals! #### ❌ WRONG: Not using gene-specific profiling denominators ```sql -- INCORRECT - Missing gene-specific denominators SELECT hugo_gene_symbol, COUNT(DISTINCT sample_unique_id) as altered_samples FROM genomic_event_derived WHERE variant_type = 'mutation' GROUP BY hugo_gene_symbol; -- Missing: WHERE ARE THE DENOMINATORS FOR EACH GENE? ``` #### ❌ WRONG: Skipping individual gene profiling queries **Problem**: Failing to run separate profiling queries for EACH gene in results. **Each gene has different coverage**: TP53 might be profiled in 25,040 samples, MUC16 in 23,000, etc. #### ✅ CORRECT: Complete gene-specific workflow ```sql -- STEP 1: Get altered counts per gene SELECT hugo_gene_symbol, entrez_gene_id, COUNT(DISTINCT CASE WHEN off_panel = 0 THEN sample_unique_id END) AS numberOfAlteredSamplesOnPanel, COUNT(*) AS totalMutationEvents FROM genomic_event_derived WHERE variant_type = 'mutation' AND mutation_status != 'UNCALLED' GROUP BY entrez_gene_id, hugo_gene_symbol ORDER BY numberOfAlteredSamplesOnPanel DESC; -- STEP 2: FOR EACH GENE, run this profiling query: SELECT COUNT(DISTINCT stgp.sample_unique_id) AS numberOfProfiledSamples FROM sample_to_gene_panel_derived stgp JOIN gene_panel gp ON stgp.gene_panel_id = gp.stable_id JOIN gene_panel_list gpl ON gp.internal_id = gpl.internal_id JOIN gene g ON gpl.gene_id = g.entrez_gene_id WHERE stgp.alteration_type = 'MUTATION_EXTENDED' AND g.hugo_gene_symbol = 'TP53' -- Replace with each gene from Step 1 AND stgp.cancer_study_identifier = 'your_study_id'; -- STEP 3: Calculate frequency = numberOfAlteredSamplesOnPanel / numberOfProfiledSamples * 100 ``` #### 🚨 WORKFLOW REQUIREMENTS VIOLATIONS: - **Missing denominator columns**: Must show gene-specific profiled samples per row - **Wrong table format**: Should be | Gene | # Mutations | # Samples | Profiled Samples | Sample % | - **Not replacing gene symbols**: Must replace 'TP53' with actual gene for each query - **Using study totals**: Never use genomic_event_derived for total sample counts ### 2. 🚨 OFF-PANEL MUTATION INCLUSION #### ❌ Wrong: Including off-panel mutations ```sql -- INCORRECT - Includes mutations outside gene panels SELEC … (37891 more chars) ◀ result {"result":[{"code":"CHOL","name":"Cholangiocarcinoma","score":80,"mainType":"Hepatobiliary Cancer","tissue":"Biliary Tract","hierarchy":"BILIARY_TRACT > IPN > CHOL"},{"code":"EHCH","name":"Extrahepatic Cholangiocarcinoma","score":50,"mainType":"Hepatobiliary Cancer","tissue":"Biliary Tract","hierarchy":"BILIARY_TRACT > IPN > CHOL > EHCH"},{"code":"HCCIHCH","name":"Hepatocellular Carcinoma plus Intrahepatic Cholangiocarcinoma","score":50,"mainType":"Hepatobiliary Cancer","tissue":"Liver","hierarchy":"LIVER > HCCIHCH"},{"code":"IHCH","name":"Intrahepatic Cholangiocarcinoma","score":50,"mainType":"Hepatobiliary Cancer","tissue":"Biliary Tract","hierarchy":"BILIARY_TRACT > IPN > CHOL > IHCH"},{"code":"PHCH","name":"Perihilar Cholangiocarcinoma","score":50,"mainType":"Hepatobiliary Cancer","tissue":"Biliary Tract","hierarchy":"BILIARY_TRACT > IPN > CHOL > PHCH"}]} ▶ list_studies { "search": "cholangiocarcinoma", "verbose": true } ▶ clickhouse_list_tables {} ◀ result {"result":[{"cancer_study_identifier":"chol_icgc_2017","name":"Cholangiocarcinoma (ICGC, Cancer Discov 2017)","description":"Whole-exome sequencing and Targeted/Exome sequencing of 489 Cholangiocarcinoma samples from 10 countries.","type_of_cancer_id":"chol","sample_count":489,"has_guide":false,"url":"https://www.cbioportal.org/study/summary?id=chol_icgc_2017"},{"cancer_study_identifier":"ihch_msk_2021","name":"Intrahepatic Cholangiocarcinoma (MSK, Hepatology 2021)","description":"Targeted sequencing of 412 intrahepatic cholangiocarcinoma tumor/normal sample pairs.","type_of_cancer_id":"ihch","sample_count":412,"has_guide":false,"url":"https://www.cbioportal.org/study/summary?id=ihch_msk_2021"},{"cancer_study_identifier":"ihch_mskcc_2020","name":"Intrahepatic Cholangiocarcinoma (MSK, Clin Cancer Res 2021)","description":"Targeted sequencing of IMPACT and CMO samples","type_of_cancer_id":"ihch","sample_count":219,"has_guide":false,"url":"https://www.cbioportal.org/study/summary?id=ihch_mskcc_2020"},{"cancer_study_identifier":"chol_msk_2018","name":"Cholangiocarcinoma (MSK, Clin Cancer Res 2018)","description":"Targeted sequencing (MSK-IMPACT) of 195 tumor samples (194 with matched normals) from 192 cholangiocarcinoma patients.","type_of_cancer_id":"chol","sample_count":195,"has_guide":false,"url":"https://www.cbioportal.org/study/summary?id=chol_msk_2018"},{"cancer_study_identifier":"hccihch_pku_2019","name":"Combined Hepatocellular and Intrahepatic Cholangiocarcinoma (Peking University, Cancer Cell 2019)","description":"Whole-exome sequencing of 121 combined hepatocellular and intrahepatic cholangiocarcinoma (cHCC-ICC) patients with matched normal pairs (whole-genome sequenced samples are not included here).","type_of_cancer_id":"hccihch","sample_count":173,"has_guide":false,"url":"https://www.cbioportal.org/study/summary?id=hccihch_pku_2019"},{"cancer_study_identifier":"ihch_smmu_2014","name":"Intrahepatic Cholangiocarcinoma (Shanghai, Nat Commun 2014)","description":"Whole exome sequencing of 103 tumor/normal sample pairs in 103 intrahepatic cholangiocarcinoma patients.","type_of_cancer_id":"ihch","sample_count":103,"has_guide":false,"url":"https://www.cbioportal.org/study/summary?id=ihch_smmu_2014"},{"cancer_study_identifier":"chol_tcga_gdc","name":"Cholangiocarcinoma (TCGA GDC, 2025)","description":"TCGA Cholangiocarcinoma. Source data from NCI GDC and generated in Aug 2025 using Cancer Data Aggregator.","type_of_cancer_id":"chol","sample_count":51,"has_guide":false,"url":"https://www.cbioportal.org/study/summary?id=chol_tcga_gdc"},{"cancer_study_identifier":"chol_tcga","name":"Cholangiocarcinoma (TCGA, Firehose Legacy)","description":"TCGA Cholangiocarcinoma. Source data from GDAC Firehose. Previously known as TCGA Provisional.","type_of_cancer_id":"chol","sam … (2172 more chars) ◀ result {"tables":[{"name":"allele_specific_copy_number"},{"name":"alteration_driver_annotation"},{"name":"cancer_study"},{"name":"cancer_study_query_preferences"},{"name":"cancer_study_tags"},{"name":"cbioportal_sequence_state"},{"name":"clinical_attribute_counts"},{"name":"clinical_attribute_meta"},{"name":"clinical_data_derived"},{"name":"clinical_event"},{"name":"clinical_event_data"},{"name":"clinical_event_data_derived"},{"name":"clinical_event_derived"},{"name":"clinical_patient"},{"name":"clinical_sample"},{"name":"cna_event"},{"name":"cna_panel_gene_coverage"},{"name":"cna_wes_coverage"},{"name":"co_altered_genes_in_study"},{"name":"copy_number_seg"},{"name":"copy_number_seg_file"},{"name":"gene"},{"name":"gene_alias"},{"name":"gene_alteration_frequency_by_cancer_type"},{"name":"gene_cna_distribution_in_study"},{"name":"gene_mutation_frequency_by_cancer_type"},{"name":"gene_mutation_frequency_in_studies"},{"name":"gene_mutation_frequency_in_study"},{"name":"gene_mutation_variants_in_study"},{"name":"gene_pair_coexpression"},{"name":"gene_panel"},{"name":"gene_panel_list"},{"name":"gene_panel_to_gene_derived"},{"name":"generic_assay_data_derived"},{"name":"generic_assay_meta_derived"},{"name":"generic_assay_profile_entity_derived"},{"name":"generic_entity_properties"},{"name":"geneset"},{"name":"geneset_gene"},{"name":"geneset_hierarchy_leaf"},{"name":"geneset_hierarchy_node"},{"name":"genetic_alteration"},{"name":"genetic_alteration_derived"},{"name":"genetic_entity"},{"name":"genetic_profile"},{"name":"genetic_profile_link"},{"name":"genetic_profile_samples"},{"name":"genomic_event_derived"},{"name":"gistic"},{"name":"gistic_to_gene"},{"name":"info"},{"name":"mut_sig"},{"name":"mutation"},{"name":"mutation_count_by_keyword"},{"name":"mutation_derived"},{"name":"mutation_event"},{"name":"mutation_panel_gene_coverage"},{"name":"mutation_wes_coverage"},{"name":"patient"},{"name":"reference_genome"},{"name":"reference_genome_gene"},{"name":"resource_definition"},{"name":"resource_patient"},{"name":"resource_sample"},{"name":"resource_study"},{"name":"sample"},{"name":"sample_cna_event"},{"name":"sample_derived"},{"name":"sample_list"},{"name":"sample_list_list"},{"name":"sample_profile"},{"name":"sample_to_gene_panel_derived"},{"name":"structural_variant"},{"name":"sv_panel_gene_coverage"},{"name":"sv_wes_coverage"},{"name":"top_cna_genes_in_study"},{"name":"top_mutated_genes_in_cohort"},{"name":"top_mutated_genes_in_study"},{"name":"top_sv_genes_in_study"},{"name":"treatment_counts_in_study"},{"name":"treatment_regimens_in_study"},{"name":"type_of_cancer"}]} ▶ clickhouse_run_select_query { "query": " SELECT cancer_study_identifier, sample_unique_id, hugo_gene_symbol, mutation_variant, mutation_type, mutation_status FROM genomic_event_derived WHERE cancer_study_identifier IN ('chol_icgc_2017', 'ihch_msk_2021', 'chol_msk_2018', 'hccihch_pku_2019', 'ihch_smmu_2014') AND hugo_gene_symbol = 'IDH1' AND variant_type = 'mutation' AND mutation_status != 'UNCALLED' AND mutation_variant NOT LIKE 'R132%' ORDER BY cancer_study_identifier, sample_unique_id, mutation_variant LIMIT 500 ", "max_rows": 500 } ◀ result {"rows":[{"cancer_study_identifier":"hccihch_pku_2019","sample_unique_id":"hccihch_pku_2019_Mix_23T","hugo_gene_symbol":"IDH1","mutation_variant":"A268S","mutation_type":"Missense_Mutation","mutation_status":"NA"},{"cancer_study_identifier":"ihch_msk_2021","sample_unique_id":"ihch_msk_2021_P-0011223-T01-IM5","hugo_gene_symbol":"IDH1","mutation_variant":"N349S","mutation_type":"Missense_Mutation","mutation_status":"SOMATIC"}]} ▶ clickhouse_run_select_query { "query": " -- Get all IDH1 mutations in major cholangiocarcinoma cohorts SELECT cancer_study_identifier, mutation_variant, mutation_type, COUNT(DISTINCT sample_unique_id) AS sample_count, COUNT(*) AS total_events FROM genomic_event_derived WHERE cancer_study_identifier IN ('chol_icgc_2017', 'ihch_msk_2021', 'chol_msk_2018', 'hccihch_pku_2019', 'ihch_smmu_2014') AND hugo_gene_symbol = 'IDH1' AND variant_type = 'mutation' AND mutation_status != 'UNCALLED' GROUP BY cancer_study_identifier, mutation_variant, mutation_type ORDER BY cancer_study_identifier, sample_count DESC ", "max_rows": 100 } ◀ result {"rows":[{"cancer_study_identifier":"chol_icgc_2017","mutation_variant":"R132C","mutation_type":"Missense_Mutation","sample_count":9,"total_events":9},{"cancer_study_identifier":"chol_icgc_2017","mutation_variant":"R132G","mutation_type":"Missense_Mutation","sample_count":4,"total_events":4},{"cancer_study_identifier":"chol_icgc_2017","mutation_variant":"R132L","mutation_type":"Missense_Mutation","sample_count":3,"total_events":3},{"cancer_study_identifier":"chol_icgc_2017","mutation_variant":"R132S","mutation_type":"Missense_Mutation","sample_count":2,"total_events":2},{"cancer_study_identifier":"chol_msk_2018","mutation_variant":"R132C","mutation_type":"Missense_Mutation","sample_count":41,"total_events":41},{"cancer_study_identifier":"chol_msk_2018","mutation_variant":"R132L","mutation_type":"Missense_Mutation","sample_count":5,"total_events":5},{"cancer_study_identifier":"chol_msk_2018","mutation_variant":"R132G","mutation_type":"Missense_Mutation","sample_count":2,"total_events":2},{"cancer_study_identifier":"hccihch_pku_2019","mutation_variant":"R132C","mutation_type":"Missense_Mutation","sample_count":3,"total_events":3},{"cancer_study_identifier":"hccihch_pku_2019","mutation_variant":"R132L","mutation_type":"Missense_Mutation","sample_count":2,"total_events":2},{"cancer_study_identifier":"hccihch_pku_2019","mutation_variant":"A268S","mutation_type":"Missense_Mutation","sample_count":1,"total_events":1},{"cancer_study_identifier":"hccihch_pku_2019","mutation_variant":"R132H","mutation_type":"Missense_Mutation","sample_count":1,"total_events":1},{"cancer_study_identifier":"ihch_msk_2021","mutation_variant":"R132C","mutation_type":"Missense_Mutation","sample_count":62,"total_events":62},{"cancer_study_identifier":"ihch_msk_2021","mutation_variant":"R132L","mutation_type":"Missense_Mutation","sample_count":15,"total_events":15},{"cancer_study_identifier":"ihch_msk_2021","mutation_variant":"R132G","mutation_type":"Missense_Mutation","sample_count":5,"total_events":5},{"cancer_study_identifier":"ihch_msk_2021","mutation_variant":"R132S","mutation_type":"Missense_Mutation","sample_count":2,"total_events":2},{"cancer_study_identifier":"ihch_msk_2021","mutation_variant":"N349S","mutation_type":"Missense_Mutation","sample_count":1,"total_events":1},{"cancer_study_identifier":"ihch_smmu_2014","mutation_variant":"R132C","mutation_type":"Missense_Mutation","sample_count":4,"total_events":4},{"cancer_study_identifier":"ihch_smmu_2014","mutation_variant":"R132L","mutation_type":"Missense_Mutation","sample_count":1,"total_events":1}]} ▶ clickhouse_run_select_query { "query": " -- Get total profiled samples for IDH1 in each study WITH idh1_profiled AS ( SELECT cancer_study_identifier, COUNT(DISTINCT sample_unique_id) AS profiled_samples FROM mutation_panel_gene_coverage WHERE cancer_study_identifier IN ('chol_icgc_2017', 'ihch_msk_2021', 'chol_msk_2018', 'hccihch_pku_2019', 'ihch_smmu_2014') AND hugo_gene_symbol = 'IDH1' GROUP BY cancer_study_identifier ) SELECT * FROM idh1_profiled ORDER BY cancer_study_identifier ", "max_rows": 100 } ◀ result {"rows":[{"cancer_study_identifier":"chol_msk_2018","profiled_samples":195},{"cancer_study_identifier":"ihch_msk_2021","profiled_samples":412}]} ▶ clickhouse_run_select_query { "query": " -- Check WES coverage for IDH1 in ICGC and other studies SELECT cancer_study_identifier, COUNT(DISTINCT sample_unique_id) AS wes_profiled_samples FROM mutation_wes_coverage WHERE cancer_study_identifier IN ('chol_icgc_2017', 'ihch_msk_2021', 'chol_msk_2018', 'hccihch_pku_2019', 'ihch_smmu_2014') GROUP BY cancer_study_identifier ORDER BY cancer_study_identifier ", "max_rows": 100 } ◀ result {"rows":[{"cancer_study_identifier":"chol_icgc_2017","wes_profiled_samples":417},{"cancer_study_identifier":"hccihch_pku_2019","wes_profiled_samples":173},{"cancer_study_identifier":"ihch_smmu_2014","wes_profiled_samples":103}]} ▶ resolve_and_route { "studyIds": [ "chol_icgc_2017", "ihch_msk_2021", "chol_msk_2018", "hccihch_pku_2019", "ihch_smmu_2014" ] } ◀ result {"success":true,"message":"Found 5 matching studies. Pick the best match (prefer TCGA → prefer PanCancer Atlas), use its metadata to call the appropriate navigation tool(s) and generate URLs immediately. Present other studies as alternatives.","data":{"totalCount":5,"studiesWithMetadata":[{"studyId":"chol_icgc_2017","name":"Cholangiocarcinoma (ICGC, Cancer Discov 2017)","sampleCount":489,"studyViewUrl":"https://www.cbioportal.org/study?id=chol_icgc_2017","metadata":{"clinicalAttributeIds":["AGE_AT_SURGERY","ANATOMICAL_SUBTYPE","CANCER_TYPE","CANCER_TYPE_DETAILED","ETHNICITY","HBV","HCV","HISTOLOGY","LIVER_FLUKE_STATUS","MUTATION_COUNT","ONCOTREE_CODE","OS_MONTHS","OS_STATUS","PSC","SAMPLE_COUNT","SEX","STAGE","TARGETED_SEQ","TMB_NONSYNONYMOUS","TNM_STAGE","WHOLE_EXOME_SEQUENCING","WHOLE_GENOME_SEQUENCING"],"molecularProfileIds":["chol_icgc_2017_mutations"],"availableComparisonTabs":["overlap","clinical","survival","alterations","mutations"]}},{"studyId":"ihch_msk_2021","name":"Intrahepatic Cholangiocarcinoma (MSK, Hepatology 2021)","sampleCount":412,"studyViewUrl":"https://www.cbioportal.org/study?id=ihch_msk_2021","metadata":{"clinicalAttributeIds":["ADJUVANT_CHEMO","AGE","BMI","CA19","CA19_HIGH","CANCER_TYPE","CANCER_TYPE_DETAILED","CHRONIC_HEPATITIS_ANY_TYPE","CIRRHOSIS","CLIN_PSC","DIABETES_STATUS","DUCT_TYPE","DZ_EXTENT","ECOG_BIN","FRACTION_GENOME_ALTERED","HAIC","HEP_B","HEP_C","LVI","MUTATION_COUNT","NEOADJ_CHEMO","ONCOTREE_CODE","OS_MONTHS","OS_MONTHS_FROM_RX","OS_STATUS","PD_INF","PNI","POSITIVE_LYMPH_NODE","POSITIVE_MARGIN","RFS_MONTHS","RFS_STATUS","SAMPLE_COUNT","SEX","SMOKING_STATUS","STEATOSIS","SYSTEMIC_CHEMO","TMB_NONSYNONYMOUS","TREATMENT_GROUP","TUMOR_GRADE","TUMOR_SIZE"],"molecularProfileIds":["ihch_msk_2021_cna","ihch_msk_2021_mutations","ihch_msk_2021_structural_variants"],"availableComparisonTabs":["overlap","clinical","survival","alterations","mutations"]}},{"studyId":"chol_msk_2018","name":"Cholangiocarcinoma (MSK, Clin Cancer Res 2018)","sampleCount":195,"studyViewUrl":"https://www.cbioportal.org/study?id=chol_msk_2018","metadata":{"clinicalAttributeIds":["AGE","AGE_AT_SEQ_REPORT","AGE_CURRENT","CANCER_TYPE","CANCER_TYPE_DETAILED","ETHNICITY","FRACTION_GENOME_ALTERED","GENE_PANEL","INSTITUTE","METASTATIC_SITE","MSI_COMMENT","MSI_SCORE","MSI_TYPE","MUTATION_COUNT","ONCOTREE_CODE","OS_MONTHS","OS_STATUS","PARTC_CONSENTED_12_245","PED_IND","POD_FIRST_LINE","PRIMARY_SITE","RACE","RECURRENCE","RELIGION","SAMPLE_CLASS","SAMPLE_COUNT","SAMPLE_COVERAGE","SAMPLE_TYPE","SEX","SOMATIC_STATUS","STAGE_4_DX","SYSTEMIC_TREATMENT","TIME_TO_LAST_FOLLOWUP","TIME_TO_METASTASIS_MONTHS","TMB_NONSYNONYMOUS","TUMOR_PURITY"],"molecularProfileIds":["chol_msk_2018_cna","chol_msk_2018_mutations","chol_msk_2018_structural_variants"],"availableComparisonTabs":["overlap","clinical","survival","alterations","mutations"]}},{"studyId":"hccihch_pku_2019","name":"Combined Hepatocellular and Intrahepatic Cholangiocarcinoma (Peking University, Cancer Cell 2 … (1917 more chars) ▶ navigate_to_results_view { "studyIds": [ "chol_icgc_2017", "ihch_msk_2021", "chol_msk_2018", "hccihch_pku_2019", "ihch_smmu_2014" ], "genes": [ "IDH1" ], "tab": "mutations" } ◀ result {"success":true,"message":"Navigating to https://www.cbioportal.org/results/mutations?cancer_study_list=chol_icgc_2017%2Cihch_msk_2021%2Cchol_msk_2018%2Chccihch_pku_2019%2Cihch_smmu_2014&gene_list=IDH1&case_set_id=all","url":"https://www.cbioportal.org/results/mutations?cancer_study_list=chol_icgc_2017%2Cihch_msk_2021%2Cchol_msk_2018%2Chccihch_pku_2019%2Cihch_smmu_2014&gene_list=IDH1&case_set_id=all","data":{"studyIds":["chol_icgc_2017","ihch_msk_2021","chol_msk_2018","hccihch_pku_2019","ihch_smmu_2014"],"studies":[{"studyId":"chol_icgc_2017","name":"Cholangiocarcinoma (ICGC, Cancer Discov 2017)","sampleCount":489},{"studyId":"ihch_msk_2021","name":"Intrahepatic Cholangiocarcinoma (MSK, Hepatology 2021)","sampleCount":412},{"studyId":"chol_msk_2018","name":"Cholangiocarcinoma (MSK, Clin Cancer Res 2018)","sampleCount":195},{"studyId":"hccihch_pku_2019","name":"Combined Hepatocellular and Intrahepatic Cholangiocarcinoma (Peking University, Cancer Cell 2019)","sampleCount":173},{"studyId":"ihch_smmu_2014","name":"Intrahepatic Cholangiocarcinoma (Shanghai, Nat Commun 2014)","sampleCount":103}],"genes":["IDH1"],"caseSetId":"all","pageDescription":"Detailed mutation table with lollipop plot showing mutation positions, types, and frequencies for queried genes."}} ═ answer (success) Perfect! Now let me create a clear summary of the findings. ## Summary: IDH1 Mutations Other Than R132 in Cholangiocarcinoma I found **2 IDH1 mutations other than R132** across major cholangiocarcinoma studies: ### Non-R132 IDH1 Variants | Mutation | Study | Sample ID | Mutation Type | Mutation Status | |----------|-------|-----------|---------------|-----------------| | **A268S** | Combined HCC-ICC (Peking University 2019) | Mix_23T | Missense | NA | | **N349S** | Intrahepatic Cholangiocarcinoma (MSK 2021) | P-0011223-T01-IM5 | Missense | Somatic | ### Complete IDH1 Mutation Profile (All Variants) **IDH1 is significantly mutated in cholangiocarcinoma**, with R132 variants dominating: | Study | Total IDH1+ Samples | Profiled Samples | Frequency | Key R132 Variants | Non-R132 Variants | |-------|-------------------|-----------------|-----------|-------------------|-------------------| | **ICGC 2017** | 18 | 417 (WES) | 4.3% | R132C (9), R132G (4), R132L (3), R132S (2) | None | | **MSK 2021 (IHCH)** | 85 | 412 | 20.6% | R132C (62), R132L (15), R132G (5), R132S (2) | **N349S (1)** | | **MSK 2018** | 48 | 195 | 24.6% | R132C (41), R132L (5), R132G (2) | None | | **Peking University 2019** | 7 | 173 (WES) | 4.0% | R132C (3), R132L (2), R132H (1) | **A268S (1)** | | **Shanghai 2014** | 5 | 103 (WES) | 4.9% | R132C (4), R132L (1) | None | ### Key Observations 1. **R132 dominance**: R132C is the most common IDH1 variant across all studies, representing the classic IDH1 hotspot 2. **Rare non-R132 variants**: Only 2 non-R132 mutations identified (A268S and N349S) out of 163 total IDH1+ samples (~1.2%) 3. **Functional significance**: Both rare variants are missense mutations at different protein positions: - **A268S** — alanine to serine substitution in the middle domain - **N349S** — asparagine to serine substitution near the C-terminus --- ## View Interactive Analysis [**Explore IDH1 mutations in cholangiocarcinoma**](https://www.cbioportal.org/results/mutations?cancer_study_list=chol_icgc_2017%2Cihch_msk_2021%2Cchol_msk_2018%2Chccihch_pku_2019%2Cihch_smmu_2014&gene_list=IDH1&case_set_id=all) This link opens the Mutations tab showing the lollipop plot of all IDH1 variants with their positions and frequencies across these 5 studies (1,372 total samples).