TY - JOUR
T1 - ZBTB33 Is Mutated in Clonal Hematopoiesis and Myelodysplastic Syndromes and Impacts RNA Splicing
AU - NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium;
AU - for the Exome Aggregation Consortium,
AU - Beauchamp, Ellen M.
AU - Leventhal, Matthew
AU - Bernard, Elsa
AU - Hoppe, Emma R.
AU - Todisco, Gabriele
AU - Creignou, Maria
AU - Gallì, Anna
AU - Castellano, Cecilia A.
AU - McConkey, Marie
AU - Tarun, Akansha
AU - Wong, Waihay
AU - Schenone, Monica
AU - Stanclift, Caroline
AU - Tanenbaum, Benjamin
AU - Malolepsza, Edyta
AU - Nilsson, Björn
AU - Bick, Alexander G.
AU - Weinstock, Joshua S.
AU - Miller, Mendy
AU - Niroula, Abhishek
AU - Dunford, Andrew
AU - Taylor-Weiner, Amaro
AU - Wood, Timothy
AU - Barbera, Alex
AU - Anand, Shankara
AU - Psaty, Bruce M.
AU - Desai, Pinkal
AU - Cho, Michael H.
AU - Johnson, Andrew D.
AU - Loos, Ruth
AU - MacArthur, Daniel G.
AU - Lek, Monkol
AU - Neuberg, Donna
AU - Lage, Kasper
AU - Carr, Steven A.
AU - Hellstrom-Lindberg, Eva
AU - Malcovati, Luca
AU - Papaemmanuil, Elli
AU - Stewart, Chip
AU - Getz, Gad
AU - Bradley, Robert K.
AU - Jaiswal, Siddhartha
AU - Ebert, Benjamin L.
N1 - Publisher Copyright:
©2021 American Association for Cancer Research.
PY - 2021/9/1
Y1 - 2021/9/1
N2 - 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 ZBTB33 as well as in YLPM1, SRCAP, and ZNF318. We also identified these mutations at low frequency in patients with myelodysplastic syndrome. Zbtb33-edited mouse hematopoietic stem and progenitor cells exhibited a competitive advantage in vivo and increased genome-wide intron retention. ZBTB33 mutations potentially link DNA methylation and RNA splicing, the two most commonly mutated pathways in clonal hematopoiesis and myelodysplastic syndromes.
AB - 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 ZBTB33 as well as in YLPM1, SRCAP, and ZNF318. We also identified these mutations at low frequency in patients with myelodysplastic syndrome. Zbtb33-edited mouse hematopoietic stem and progenitor cells exhibited a competitive advantage in vivo and increased genome-wide intron retention. ZBTB33 mutations potentially link DNA methylation and RNA splicing, the two most commonly mutated pathways in clonal hematopoiesis and myelodysplastic syndromes.
UR - http://www.scopus.com/inward/record.url?scp=85130748039&partnerID=8YFLogxK
U2 - 10.1158/2643-3230.BCD-20-0224
DO - 10.1158/2643-3230.BCD-20-0224
M3 - Article
C2 - 34568833
AN - SCOPUS:85130748039
SN - 2643-3230
VL - 2
SP - 500
EP - 517
JO - Blood Cancer Discovery
JF - Blood Cancer Discovery
IS - 5
ER -