{"doi":"10.1001/jamanetworkopen.2020.28644","title":"Spectrum of Somatic Cancer Gene Variations Among Adults With Appendiceal Cancer by Age","abstract":"Importance: The incidence of appendiceal cancer (AC) is rising, particularly among individuals younger than 50 years (early-onset AC), with unexplained etiologies. The unique spectrum of somatic cancer gene variations among patients with early-onset AC is largely undetermined. Objective: To characterize the frequency of somatic variations and genomic patterns among patients with early-onset (age <50 years) vs late-onset (age ≥50 years) AC. Design, Setting, and Participants: This cohort study included individuals aged 18 years and older diagnosed with pathologically verified AC. Cases with clinical-grade targeted sequencing data from January 1, 2011, to December 31, 2019, were identified from the international clinicogenomic data-sharing consortium American Association for Cancer Research Project Genomics Evidence Neoplasia Information Exchange (GENIE). Data analysis was conducted from May to September 2020. Exposures: Age at disease onset. Main Outcomes and Measures: Somatic variation prevalence and spectrum in AC patients was determined. Variation comparisons between early-onset and late-onset AC were evaluated using multivariable logistic regression with adjustment for sex, race/ethnicity, histological subtype, sequencing center, and sample type. Results: In total 385 individuals (mean [SD] age at diagnosis, 56.0 [12.4] years; 187 [48.6%] men; 306 [79.5%] non-Hispanic White individuals) with AC were included in this study, and 109 patients (28.3%) were diagnosed with early-onset AC. Race/ethnicity differed by age at disease onset; non-Hispanic Black individuals accounted for a larger proportion of early-onset vs late-onset cases (9 of 109 [8.3%] vs 11 of 276 [4.0%]; P = 0.04). Compared with patients aged 50 years or older at diagnosis, patients with early-onset AC had significantly higher odds of presenting with nonsilent variations in PIK3CA, SMAD3, and TSC2 (PIK3CA: odds ratio [OR], 4.58; 95% CI, 1.72-12.21; P = .002; SMAD3: OR, 7.37; 95% CI, 1.24-43.87; P = .03; TSC2: OR, 12.43; 95% CI, 1.03-149.59; P = .047). In contrast, patients with early-onset AC had a 60% decreased odds of presenting with GNAS nonsilent variations compared with patients with late-onset AC (OR, 0.40; 95% CI, 0.21-0.76, P = .006). By histological subtype, young patients with mucinous adenocarcinomas of the appendix had 65% decreased odds of variations in GNAS compared with late-onset cases in adjusted models (OR, 0.35; 95% CI, 0.15-0.79; P = .01). Similarly, patients with early-onset nonmucinous appendiceal adenocarcinomas had 72% decreased odds of presenting with GNAS variations vs late-onset cases, although these findings did not reach significance (OR, 0.28; 95% CI, 0.07-1.14; P = .08). GNAS and TP53 variations were mutually exclusive in ACs among early-onset and late-onset cases (P < .05). Conclusions and Relevance: In the study, AC diagnosed among younger individuals harbored a distinct genomic landscape compared with AC diagnosed among older individuals. Development of therapeutic modalities that target these unique molecular features may yield clinical implications specifically for younger patients.","journal":"JAMA Network Open","year":2020,"id":105142,"datarank":0.48283137373023016,"base_score":3.2188758248682006,"endowment":3.2188758248682006,"self_citation_contribution":0.48283137373023016,"citation_network_contribution":0.0,"self_endowment_contribution":0.48283137373023016,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":24,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9434,"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":332456,"name":"Cathy Eng","orcid":"0000-0003-2335-0612","position":1,"is_corresponding":false},{"id":259911,"name":"Wanqing Wen","orcid":"0000-0002-3004-5168","position":2,"is_corresponding":false},{"id":298992,"name":"Kamran Idrees","orcid":"0000-0003-0911-4461","position":3,"is_corresponding":false},{"id":240064,"name":"Xingyi Guo","orcid":"0000-0001-5269-1294","position":4,"is_corresponding":false},{"id":372477,"name":"Andreana N. Holowatyj","orcid":"0000-0001-8001-8793","position":0,"is_corresponding":true}],"reference_count":63,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:12:17.683386Z","pmid":"33295976","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":[]}