{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Zhao J"],"funding":["New York Stem Cell Foundation","Cancer Research UK","Alex's Lemonade Stand Foundation for Childhood Cancer","NIDDK NIH HHS","Howard Hughes Medical Institute","MPN Research Foundation","NHLBI NIH HHS","Medical Research Council","NCI NIH HHS","National Institutes of Health","Edward P. Evans Foundation","Leukemia and Lymphoma Society"],"pagination":["642-658.e19"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10872907"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["187(3)"],"pubmed_abstract":["Despite advances in defining diverse somatic mutations that cause myeloid malignancies, a significant heritable component for these cancers remains largely unexplained. Here, we perform rare variant association studies in a large population cohort to identify inherited predisposition genes for these blood cancers. CTR9, which encodes a key component of the PAF1 transcription elongation complex, is among the significant genes identified. The risk variants found in the cases cause loss of function and result in a ∼10-fold increased odds of acquiring a myeloid malignancy. Partial CTR9 loss of function expands human hematopoietic stem cells (HSCs) by increased super elongation complex-mediated transcriptional activity, which thereby increases the expression of key regulators of HSC self-renewa"],"journal":["Cell"],"pubmed_title":["Inherited blood cancer predisposition through altered transcription elongation."],"pmcid":["PMC10872907"],"funding_grant_id":["R01 DK103794","P01 CA066996","R01 HL146500","RCCASF-May22\\100002","T32 HL007574","MC_PC_17230","R01 CA265726"],"pubmed_authors":["Arora UP","Cato LD","Williams N","Nangalia J","Sankaran VG","Goldman SR","Erb MA","Armstrong SA","Vos SM","Bryant SC","Jia Y","Zhao J","Bao EL"],"additional_accession":[]},"is_claimable":false,"name":"Inherited blood cancer predisposition through altered transcription elongation.","description":"Despite advances in defining diverse somatic mutations that cause myeloid malignancies, a significant heritable component for these cancers remains largely unexplained. Here, we perform rare variant association studies in a large population cohort to identify inherited predisposition genes for these blood cancers. CTR9, which encodes a key component of the PAF1 transcription elongation complex, is among the significant genes identified. The risk variants found in the cases cause loss of function and result in a ∼10-fold increased odds of acquiring a myeloid malignancy. Partial CTR9 loss of function expands human hematopoietic stem cells (HSCs) by increased super elongation complex-mediated transcriptional activity, which thereby increases the expression of key regulators of HSC self-renewa","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Feb","modification":"2026-06-02T11:57:35.241Z","creation":"2025-04-03T23:23:42.34Z"},"accession":"S-EPMC10872907","cross_references":{"pubmed":["38218188"],"doi":["10.1016/j.cell.2023.12.016"]}}