Discovery of regulatory noncoding variants in individual cancer genomes by using cis-X.

Autor: Liu Y; Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China. liuyu@scmc.com.cn.; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA. liuyu@scmc.com.cn., Li C; Department of Tumor Cell Biology, St. Jude Children's Research Hospital, Memphis, TN, USA., Shen S; Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.; Key Laboratory of Pediatric Hematology & Oncology Ministry of Health, Department of Hematology & Oncology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China., Chen X; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA., Szlachta K; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA., Edmonson MN; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA., Shao Y; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA., Ma X; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA., Hyle J; Department of Tumor Cell Biology, St. Jude Children's Research Hospital, Memphis, TN, USA., Wright S; Department of Tumor Cell Biology, St. Jude Children's Research Hospital, Memphis, TN, USA., Ju B; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA., Rusch MC; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA., Liu Y; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA., Li B; Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.; Key Laboratory of Pediatric Hematology & Oncology Ministry of Health, Department of Hematology & Oncology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China., Macias M; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA., Tian L; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA., Easton J; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA., Qian M; Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, TN, USA., Yang JJ; Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, TN, USA.; Hematological Malignancies Program, St. Jude Children's Research Hospital, Memphis, TN, USA.; Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN, USA., Hu S; Children's Hospital of Soochow University, Suzhou, China., Look AT; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.; Division of Pediatric Hematology-Oncology, Boston Children's Hospital, Boston, MA, USA., Zhang J; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA. jinghui.zhang@stjude.org.
Jazyk: angličtina
Zdroj: Nature genetics [Nat Genet] 2020 Aug; Vol. 52 (8), pp. 811-818. Date of Electronic Publication: 2020 Jul 06.
DOI: 10.1038/s41588-020-0659-5
Abstrakt: We developed cis-X, a computational method for discovering regulatory noncoding variants in cancer by integrating whole-genome and transcriptome sequencing data from a single cancer sample. cis-X first finds aberrantly cis-activated genes that exhibit allele-specific expression accompanied by an elevated outlier expression. It then searches for causal noncoding variants that may introduce aberrant transcription factor binding motifs or enhancer hijacking by structural variations. Analysis of 13 T-lineage acute lymphoblastic leukemias identified a recurrent intronic variant predicted to cis-activate the TAL1 oncogene, a finding validated in vivo by chromatin immunoprecipitation sequencing of a patient-derived xenograft. Candidate oncogenes include the prolactin receptor PRLR activated by a focal deletion that removes a CTCF-insulated neighborhood boundary. cis-X may be applied to pediatric and adult solid tumors that are aneuploid and heterogeneous. In contrast to existing approaches, which require large sample cohorts, cis-X enables the discovery of regulatory noncoding variants in individual cancer genomes.
Databáze: MEDLINE
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