{"doi":"10.1111/cas.16262","title":"Clinicopathological, molecular, and prognostic features of colorectal carcinomas with <scp><i>KRAS</i></scp> c.<scp>34G</scp>&gt;T (p.<scp>G12C</scp>) mutation","abstract":"Abstract Evidence indicates that combinations of anti‐EGFR antibodies and KRAS p.G12C (c.34G&gt;T) inhibitors can be an effective treatment strategy for advanced colorectal cancer. We hypothesized that KRAS c.34G&gt;T (p.G12C)‐mutated colorectal carcinoma might be a distinct tumor subtype. We utilized a prospective cohort incident tumor biobank (including 1347 colorectal carcinomas) and detected KRAS c.34G&gt;T (p.G12C) mutation in 43 cases (3.2%) and other KRAS mutations (in codon 12, 13, 61, or 146) in 467 cases (35%). The CpG island methylator phenotype (CIMP)‐low prevalence was similarly higher in KRAS c.34G&gt;T mutants (52%) and other KRAS mutants (49%) than in KRAS ‐wild‐type tumors (31%). KRAS c.34G&gt;T mutants showed higher CIMP‐high prevalence (14%) and lower CIMP‐negative prevalence (33%) compared with other KRAS mutants (6% and 45%, respectively; p = 0.0036). Similar to other KRAS mutants, KRAS c.34G&gt;T‐mutated tumors were associated with cecal location, non‐microsatellite instability (MSI)‐high status, BRAF wild type, and PIK3CA mutation when compared with KRAS ‐wild‐type tumors. Compared with BRAF ‐mutated tumors, KRAS c.34G&gt;T mutants showed more frequent LINE‐1 hypomethylation, a biomarker for early‐onset colorectal carcinoma. KRAS c.34G&gt;T mutants were not associated with other features, including the tumor tissue abundance of Fusobacterium nucleatum ( F. animalis ), pks + Escherichia coli , Bifidobacterium , or (enterotoxigenic) Bacteroides fragilis . Among 1122 BRAF ‐wild‐type colorectal carcinomas, compared with KRAS ‐wild‐type tumors, multivariable‐adjusted colorectal cancer‐specific mortality hazard ratios (95% confidence interval) were 1.82 (1.05–3.17) in KRAS c.34G&gt;T (p.G12C)‐mutated tumors ( p = 0.035) and 1.57 (1.22–2.02) in other KRAS ‐mutated tumors ( p = 0.0004). Our study provides novel evidence for clinical and tumor characteristics of KRAS c.34G&gt;T (p.G12C)‐mutated colorectal carcinoma.","journal":"Cancer Science","year":2024,"id":456235,"datarank":0.29188652235829704,"base_score":1.9459101490553132,"endowment":1.9459101490553132,"self_citation_contribution":0.29188652235829704,"citation_network_contribution":0.0,"self_endowment_contribution":0.29188652235829704,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9106,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1280662,"name":"Qian Yao","orcid":"0009-0007-4299-2510","position":1,"is_corresponding":false},{"id":665246,"name":"Yasutoshi Takashima","orcid":"0009-0009-0430-454X","position":2,"is_corresponding":false},{"id":1280663,"name":"Yuxue Zhong","orcid":"0009-0007-5718-7549","position":3,"is_corresponding":false},{"id":1280664,"name":"Kosuke Matsuda","orcid":"0009-0002-7513-038X","position":4,"is_corresponding":false},{"id":1093845,"name":"Hidetaka Kawamura","orcid":null,"position":5,"is_corresponding":false},{"id":1043226,"name":"Yu Imamura","orcid":"0000-0002-0036-0124","position":6,"is_corresponding":false},{"id":849136,"name":"Kazuo Okadome","orcid":"0000-0002-8148-0290","position":7,"is_corresponding":false},{"id":333369,"name":"Kosuke Mima","orcid":"0000-0002-4385-4984","position":8,"is_corresponding":false},{"id":243704,"name":"Kota Arima","orcid":null,"position":9,"is_corresponding":false},{"id":333370,"name":"Keisuke Kosumi","orcid":"0000-0003-4028-1137","position":10,"is_corresponding":false},{"id":104568,"name":"Mingyang Song","orcid":"0000-0002-1324-0316","position":11,"is_corresponding":false},{"id":6441,"name":"Jeffrey A. Meyerhardt","orcid":"0000-0002-1120-0898","position":12,"is_corresponding":false},{"id":3011,"name":"Marios Giannakis","orcid":"0000-0001-9012-6982","position":13,"is_corresponding":false},{"id":3733,"name":"Jonathan A. Nowak","orcid":"0000-0002-0943-7407","position":14,"is_corresponding":false},{"id":241016,"name":"Tomotaka Ugai","orcid":"0000-0003-0182-5269","position":15,"is_corresponding":false},{"id":3732,"name":"Shuji Ogino","orcid":"0000-0002-3909-2323","position":16,"is_corresponding":false},{"id":1093432,"name":"Satoko Ugai","orcid":"0009-0001-9661-9363","position":0,"is_corresponding":true}],"reference_count":61,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:03:27.785212Z","pmid":"39039804","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}