Genetic alterations of m6A regulators predict poorer survival in acute myeloid leukemia.
Methylation of N6adenosine (m6A) is known to be important for diverse biological processes including gene expression control, translation of protein, and messenger RNA (mRNA) splicing. However, its role in the development of human cancers is poorly understood. By analyzing datasets from the Cancer Genome Atlas Research Network (TCGA) acute myeloid leukemia (AML) study, we discover that mutations and/or copy number variations of m6A regulatory genes are strongly associated with the presence of TP53 mutations in AML patients. Further, our analyses reveal that alterations in m6A regulatory genes confer a worse survival in AML. Our work indicates that genetic alterations of m6A regulatory genes may cooperate with TP53 and/or its regulator/downstream targets in the pathogenesis and/or maintenance of AML.
Gene & Stem Cell Therapy Program, Centenary Institute, University of Sydney, Camperdown, 2050, Australia.|Gene Regulation in Cancer Laboratory, Centenary Institute, University of Sydney, Camperdown, 2050, Australia.|Sydney Medical School, University of Sydney, Camperdown, NSW, 2006, Australia.
Chau-To
CT
Kwok
Gene & Stem Cell Therapy Program, Centenary Institute, University of Sydney, Camperdown, 2050, Australia.|Sydney Medical School, University of Sydney, Camperdown, NSW, 2006, Australia.
Amy D
AD
Marshall
Gene & Stem Cell Therapy Program, Centenary Institute, University of Sydney, Camperdown, 2050, Australia.|Sydney Medical School, University of Sydney, Camperdown, NSW, 2006, Australia.|Cell and Molecular Therapies, Royal Prince Alfred Hospital, Camperdown, 2050, Australia.
John E J
JE
Rasko
Gene & Stem Cell Therapy Program, Centenary Institute, University of Sydney, Camperdown, 2050, Australia. j.wong@centenary.org.au.|Gene Regulation in Cancer Laboratory, Centenary Institute, University of Sydney, Camperdown, 2050, Australia. j.wong@centenary.org.au.|Sydney Medical School, University of Sydney, Camperdown, NSW, 2006, Australia. j.wong@centenary.org.au.
Justin J L
JJ
Wong
D000241:Adenosine / Q000031:analogs & derivatives* / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018572:Disease-Free Survival; D005260:Female; D005784:Gene Amplification; D015973:Gene Expression Regulation, Leukemic; D016158:Genes, p53; D006801:Humans; D053208:Kaplan-Meier Estimate; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D008297:Male; D008745:Methylation; D008875:Middle Aged; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000378:metabolism*; D017384:Sequence Deletion; D055815:Young Adult
D009363:Neoplasm Proteins; D012333:RNA, Messenger; C054123:N(6)-ribosyladenine; D000241:Adenosine
Acute myeloid leukemia; Leukemia; RNA modification; TP53 mutation; m6A