{"doi":"10.1016/j.celrep.2021.108707","title":"Whole-genome characterization of lung adenocarcinomas lacking alterations in the RTK/RAS/RAF pathway","abstract":"RTK/RAS/RAF pathway alterations (RPAs) are a hallmark of lung adenocarcinoma (LUAD). In this study, we use whole-genome sequencing (WGS) of 85 cases found to be RPA(-) by previous studies from The Cancer Genome Atlas (TCGA) to characterize the minority of LUADs lacking apparent alterations in this pathway. We show that WGS analysis uncovers RPA(+) in 28 (33%) of the 85 samples. Among the remaining 57 cases, we observe focal deletions targeting the promoter or transcription start site of STK11 (n = 7) or KEAP1 (n = 3), and promoter mutations associated with the increased expression of ILF2 (n = 6). We also identify complex structural variations associated with high-level copy number amplifications. Moreover, an enrichment of focal deletions is found in TP53 mutant cases. Our results indicate that RPA(-) cases demonstrate tumor suppressor deletions and genome instability, but lack unique or recurrent genetic lesions compensating for the lack of RPAs. Larger WGS studies of RPA(-) cases are required to understand this important LUAD subset.","journal":"Cell Reports","year":2021,"id":167114,"datarank":1.1424222951548462,"base_score":3.4965075614664802,"endowment":3.4965075614664802,"self_citation_contribution":0.5244761342199721,"citation_network_contribution":0.617946160934874,"self_endowment_contribution":0.5244761342199721,"citer_contribution":0.617946160934874,"corpus_percentile":null,"corpus_rank":null,"citation_count":32,"citer_count":23,"citers_with_citation_signal":19,"citers_with_endowment":19,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8633,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":14254,"name":"Xiaotong Yao","orcid":"0000-0002-5140-6639","position":1,"is_corresponding":false},{"id":518148,"name":"Siddhartha Devarakonda","orcid":"0000-0003-2693-3848","position":2,"is_corresponding":false},{"id":693872,"name":"Aditya Deshpande","orcid":"0000-0002-4463-2697","position":3,"is_corresponding":false},{"id":52027,"name":"Jeffrey S. 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