{"doi":"10.1101/2021.07.08.451695","title":"Allele-specific expression links diverse cis-regulatory mutations to recurrent gene dysregulation in high-risk neuroblastoma","abstract":"Abstract Neuroblastoma is a pediatric malignancy with a high frequency of metastatic disease at initial diagnosis. Neuroblastoma tumors have few protein-coding mutations but contain extensive somatic copy number alterations (SCNAs) suggesting that mutations that alter gene dosage are important drivers of tumorigenesis. Here we analyze allele-specific expression (ASE) in 96 high-risk neuroblastoma tumors to discover genes with cis-acting mutations that alter dosage. We identify 1,049 genes with recurrent, neuroblastoma-specific ASE, 68% of which lie within common SCNA regions. However, many genes exhibit ASE in copy neutral samples and are enriched for mutations that cause nonsense-mediated decay, indicating that neuroblastoma tumors select for multiple types of mutations that alter gene expression. We also find 24 genes with reduced expression in stage 4 disease that have neuroblastoma-specific ASE that is independent of SCNAs. At least two of these genes have evidence for tumor suppressor activity including the transcription factor TFAP2B and the protein tyrosine phosphatase PTPRH . In summary, our ASE analysis discovers genes that are recurrently dysregulated by both large SCNAs and other cis-acting mutations in high-risk neuroblastoma.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":225649,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9545,"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":828810,"name":"Yuchen Huo","orcid":null,"position":1,"is_corresponding":false},{"id":828382,"name":"Jennifer Elster","orcid":"0000-0003-4718-7266","position":2,"is_corresponding":false},{"id":460921,"name":"Peter E. Zage","orcid":"0000-0003-1837-2315","position":3,"is_corresponding":false},{"id":43077,"name":"Graham McVicker","orcid":"0000-0003-0991-0951","position":4,"is_corresponding":false},{"id":749708,"name":"Arko Sen","orcid":"0000-0001-9876-281X","position":0,"is_corresponding":true}],"reference_count":70,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:54:30.292454Z","pmid":null,"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":[]}