{"doi":"10.1371/journal.pone.0234505","title":"Comparative genomics of high grade neuroendocrine carcinoma of the cervix","abstract":"In order to improve treatment selection for high grade neuroendocrine carcinomas of the cervix (NECC), we performed a comparative genomic analysis between this rare tumor type and other cervical cancer types, as well as extra-cervical neuroendocrine small cell carcinomas of the lung and bladder. We performed whole exome sequencing on fresh-frozen tissue from 15 NECCs and matched normal tissue. We then identified mutations and copy number variants using standard analysis pipelines. Published mutation tables from cervical cancers and extra-cervical small cell carcinomas were used for comparative analysis. Descriptive statistical methods were used and a two-sided threshold of P < .05 was used for significance. In the NECC cohort, we detected a median of 1.7 somatic mutations per megabase (range 1.0-20.9). PIK3CA p.E545K mutations were the most frequency observed oncogenic mutation (4/15 tumors, 27%). Activating MAPK pathway mutations in KRAS (p.G12D) and GNAS (p.R201C) co-occurred in two tumors (13%). In total we identified PI3-kinase or MAPK pathway activating mutations in 67% of NECC. When compared to NECC, lung and bladder small cell carcinomas exhibited a statistically significant higher rate of coding mutations (P < .001 for lung; P = .001 for bladder). Mutation of TP53 was uncommon in NECC (13%) and was more frequent in both lung (103 of 110 tumors [94%], P < .001) and bladder (18 of 19 tumors [95%], P < .001) small cell carcinoma. These comparative genomics data suggest that NECC may be genetically more similar to common cervical cancer subtypes than to extra-cervical small cell neuroendocrine carcinomas of the lung and bladder. These results may have implications for the selection of cytotoxic and targeted therapy regimens for this rare disease.","journal":"PLoS ONE","year":2020,"id":92455,"datarank":0.5676284450877392,"base_score":3.784189633918261,"endowment":3.784189633918261,"self_citation_contribution":0.5676284450877392,"citation_network_contribution":0.0,"self_endowment_contribution":0.5676284450877392,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":43,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8975,"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":348530,"name":"Robert J. Cardnell","orcid":"0009-0005-6203-0234","position":1,"is_corresponding":false},{"id":69930,"name":"Junya Fujimoto","orcid":"0000-0003-4813-3163","position":2,"is_corresponding":false},{"id":268274,"name":"Won-Chul Lee","orcid":"0000-0003-3913-8632","position":3,"is_corresponding":false},{"id":5677,"name":"Jianjun Zhang","orcid":"0000-0001-7872-3477","position":4,"is_corresponding":false},{"id":228166,"name":"Lauren A. Byers","orcid":"0000-0002-0780-2677","position":5,"is_corresponding":false},{"id":424986,"name":"Preetha Ramalingam","orcid":"0000-0002-4816-507X","position":6,"is_corresponding":false},{"id":298567,"name":"Mario M. Leitão","orcid":"0000-0003-0818-3836","position":7,"is_corresponding":false},{"id":70261,"name":"Elizabeth M. Swisher","orcid":"0000-0003-2331-0434","position":8,"is_corresponding":false},{"id":7944,"name":"P. Andrew Futreal","orcid":"0000-0001-8663-2671","position":9,"is_corresponding":false},{"id":256630,"name":"Michael Frumovitz","orcid":"0000-0002-0810-2648","position":10,"is_corresponding":false},{"id":459566,"name":"R. Tyler Hillman","orcid":"0000-0002-9832-9925","position":0,"is_corresponding":true}],"reference_count":39,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T22:30:31.563852Z","pmid":"32544169","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":[]}