{"doi":"10.1093/jnci/djaa133","title":"Genome-Wide Association Study of Susceptibility Loci for <i>TCF3-PBX1</i> Acute Lymphoblastic Leukemia in Children","abstract":"Abstract Acute lymphoblastic leukemia (ALL) is the most common cancer in children. TCF3-PBX1 fusion defines a common molecular subtype of ALL with unique clinical features, but the molecular basis of its inherited susceptibility is unknown. In a genome-wide association study of 1494 ALL cases and 2057 non-ALL controls, we identified a germline risk locus located in an intergenic region between BCL11A and PAPOLG: rs2665658, P = 1.88 × 10–8 for TCF3-PBX1 ALL vs non-ALL, and P = 1.70 × 10–8 for TCF3-PBX1 ALL vs other-ALL. The lead variant was validated in a replication cohort, and conditional analyses pointed to a single causal variant with subtype-specific effect. The risk variant is located in a regulatory DNA element uniquely activated in ALL cells with the TCF3-PBX1 fusion and may distally modulate the transcription of the adjacent gene REL. Our results expand the understanding of subtype-specific ALL susceptibility and highlight plausible interplay between germline variants and somatic genomic abnormalities in ALL pathogenesis.","journal":"JNCI Journal of the National Cancer Institute","year":2020,"id":82449,"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":13,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9501,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"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":301501,"name":"Maoxiang Qian","orcid":"0000-0003-2889-546X","position":1,"is_corresponding":false},{"id":24352,"name":"Wentao Yang","orcid":"0000-0001-7712-822X","position":2,"is_corresponding":false},{"id":285756,"name":"Jonathan D. Diedrich","orcid":"0000-0001-6178-9584","position":3,"is_corresponding":false},{"id":271728,"name":"Elizabeth A. Raetz","orcid":"0000-0002-8547-1658","position":4,"is_corresponding":false},{"id":262379,"name":"Wenjian Yang","orcid":"0000-0002-7305-5649","position":5,"is_corresponding":false},{"id":425623,"name":"Qian Dong","orcid":"0000-0001-9140-2870","position":6,"is_corresponding":false},{"id":355165,"name":"Meenakshi Devidas","orcid":"0000-0002-1099-3478","position":7,"is_corresponding":false},{"id":248828,"name":"Deqing Pei","orcid":null,"position":8,"is_corresponding":false},{"id":262397,"name":"Allen Eng Juh Yeoh","orcid":"0000-0002-6454-976X","position":9,"is_corresponding":false},{"id":247443,"name":"Cheng Cheng","orcid":"0000-0002-5401-6185","position":10,"is_corresponding":false},{"id":254773,"name":"Ching‐Hon Pui","orcid":"0000-0003-0303-5658","position":11,"is_corresponding":false},{"id":258247,"name":"William E. Evans","orcid":"0000-0002-9333-5322","position":12,"is_corresponding":false},{"id":247450,"name":"Charles G. Mullighan","orcid":"0000-0002-1871-1850","position":13,"is_corresponding":false},{"id":301503,"name":"Stephen P. Hunger","orcid":"0000-0002-5492-3957","position":14,"is_corresponding":false},{"id":43149,"name":"Daniel Savic","orcid":"0000-0002-6693-0265","position":15,"is_corresponding":false},{"id":258248,"name":"Mary V. Relling","orcid":"0000-0002-3720-9591","position":16,"is_corresponding":false},{"id":301504,"name":"Mignon L. Loh","orcid":"0000-0003-4099-4700","position":17,"is_corresponding":false},{"id":107683,"name":"Jun J. Yang","orcid":"0000-0002-0770-9659","position":18,"is_corresponding":false},{"id":427007,"name":"Shawn H. R. Lee","orcid":null,"position":0,"is_corresponding":true}],"reference_count":25,"raw_metadata":null,"created_at":"2026-07-18T21:53:48.608934Z","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":[]}