02637nas a2200673 4500008004100000022001400041245009500055210006900150260001300219300001200232490000600244520068400250100002400934700002300958700001800981700001900999700002201018700002001040700001701060700002701077700002001104700001901124700001701143700002101160700002401181700002401205700002201229700002001251700002301271700002501294700001801319700002201337700002001359700002501379700001801404700001801422700002001440700002001460700001801480700002001498700002301518700001501541700002501556700001601581700002201597700001701619700002001636700002801656700002001684700002301704700001801727700001401745700002301759700002401782700002301806710006501829710003301894856003601927 2021 eng d a2643-324900ais mutated in clonal hematopoiesis and myelodysplastic syndromes and impacts RNA splicing.0 amutated in clonal hematopoiesis and myelodysplastic syndromes an c2021 Sep a500-5170 v23 a
Clonal hematopoiesis results from somatic mutations in cancer driver genes in hematopoietic stem cells. We sought to identify novel drivers of clonal expansion using an unbiased analysis of sequencing data from 84,683 persons and identified common mutations in the 5-methylcytosine reader, , as well as in , , and . We also identified these mutations at low frequency in myelodysplastic syndrome patients. edited mouse hematopoietic stem and progenitor cells exhibited a competitive advantage and increased genome-wide intron retention. mutations potentially link DNA methylation and RNA splicing, the two most commonly mutated pathways in clonal hematopoiesis and MDS.
1 aBeauchamp, Ellen, M1 aLeventhal, Matthew1 aBernard, Elsa1 aHoppe, Emma, R1 aTodisco, Gabriele1 aCreignou, Maria1 aGallì, Anna1 aCastellano, Cecilia, A1 aMcConkey, Marie1 aTarun, Akansha1 aWong, Waihay1 aSchenone, Monica1 aStanclift, Caroline1 aTanenbaum, Benjamin1 aMalolepsza, Edyta1 aNilsson, Björn1 aBick, Alexander, G1 aWeinstock, Joshua, S1 aMiller, Mendy1 aNiroula, Abhishek1 aDunford, Andrew1 aTaylor-Weiner, Amaro1 aWood, Timothy1 aBarbera, Alex1 aAnand, Shankara1 aPsaty, Bruce, M1 aDesai, Pinkal1 aCho, Michael, H1 aJohnson, Andrew, D1 aLoos, Ruth1 aMacArthur, Daniel, G1 aLek, Monkol1 aNeuberg, Donna, S1 aLage, Kasper1 aCarr, Steven, A1 aHellstrom-Lindberg, Eva1 aMalcovati, Luca1 aPapaemmanuil, Elli1 aStewart, Chip1 aGetz, Gad1 aBradley, Robert, K1 aJaiswal, Siddhartha1 aEbert, Benjamin, L1 aNHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium1 aExome Aggregation Consortium uhttps://chs-nhlbi.org/node/8908