{"doi":"10.1038/s41416-020-1015-3","title":"Integrated clinico-molecular profiling of appendiceal adenocarcinoma reveals a unique grade-driven entity distinct from colorectal cancer","abstract":"BACKGROUND: Appendiceal adenocarcinoma (AA) is an orphan disease with unique clinical attributes but often treated as colorectal cancer (CRC). Understanding key molecular differences between AA and CRC is critical. METHODS: We performed retrospective analyses of AA patients (N = 266) with tumour and/or blood next-generation sequencing (NGS) (2013-2018) with in-depth clinicopathological annotation. Overall survival (OS) was examined. For comparison, CRC cohorts annotated for sidedness, consensus molecular subtypes (CMS) and mutations (N = 3283) were used. RESULTS: Blood-NGS identified less RAS/GNAS mutations compared to tissue-NGS (4.2% vs. 60.9%, P < 0.0001) and showed poor concordance with tissue for well-/moderately differentiated tumours. RAS (56.2%), GNAS (28.1%) and TP53 (26.9%) were most frequent mutations. Well/moderately differentiated tumours harboured more RAS (69.2%/64.0% vs. 40.5%) and GNAS (48.7%/32.0% vs. 10.1%) while moderate/poorly differentiated tumours had more TP53 (26.0%/27.8% vs. 7.7%) mutations. Appendiceal adenocarcinoma (compared to CRC) harboured significantly fewer APC (9.1% vs. 55.4%) and TP53 (26.9% vs. 67.5%) and more GNAS mutations (28.1% vs. 2.0%) (P < 0.0001). Appendiceal adenocarcinoma mutation profile did not resemble either right-sided CRC or any of the four CMS in CRC. High grade, but no mutation, was independently predictive of survival. CONCLUSION: Integrated clinico-molecular profiling of AA identified key molecular drivers distinct from CRC. Appendiceal adenocarcinoma has a predominantly grade-driven biology that trumps mutations.","journal":"British Journal of Cancer","year":2020,"id":62908,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":48,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9283,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":308739,"name":"John Paul Shen","orcid":"0000-0003-4588-2775","position":1,"is_corresponding":false},{"id":332452,"name":"Alexandre A. Jácome","orcid":"0000-0001-9070-4383","position":2,"is_corresponding":false},{"id":333263,"name":"Jennifer L. Guerra","orcid":null,"position":3,"is_corresponding":false},{"id":333264,"name":"Christopher P. Scally","orcid":null,"position":4,"is_corresponding":false},{"id":318551,"name":"Melissa W. Taggart","orcid":"0000-0002-7803-9904","position":5,"is_corresponding":false},{"id":332453,"name":"Wai Chin Foo","orcid":"0000-0002-0471-4911","position":6,"is_corresponding":false},{"id":332454,"name":"Aurelio Matamoros","orcid":"0000-0002-0068-3679","position":7,"is_corresponding":false},{"id":1948,"name":"Kenna Shaw","orcid":"0000-0002-6873-0793","position":8,"is_corresponding":false},{"id":332455,"name":"Keith F. Fournier","orcid":"0000-0002-7882-9826","position":9,"is_corresponding":false},{"id":274184,"name":"Michael J. Overman","orcid":"0000-0001-5377-135X","position":10,"is_corresponding":false},{"id":332456,"name":"Cathy Eng","orcid":"0000-0003-2335-0612","position":11,"is_corresponding":false},{"id":264370,"name":"Kanwal Raghav","orcid":"0000-0003-1311-4173","position":0,"is_corresponding":true}],"reference_count":48,"raw_metadata":null,"created_at":"2026-07-18T21:10:35.996198Z","pmid":"32733093","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":[]}