title: Molecular features of early onset adult myelodysplastic syndrome.
abstract: Myelodysplastic syndromes are typically diseases of older adults. Patients in whom the onset is early may have distinct molecular and clinical features or reflect a demographic continuum. The identification of differences between "early onset" patients and those diagnosed at a traditional age has the potential to advance understanding of the pathogenesis of myelodysplasia and may lead to formation of distinct morphological subcategories. We studied a cohort of 634 patients with various subcategories of myelodysplastic syndrome and secondary acute myeloid leukemia, stratifying them based on age at presentation and clinical parameters. We then characterized molecular abnormalities detected by next-generation deep sequencing of 60 genes that are commonly mutated in myeloid malignancies. The number of mutations increased linearly with age and on average, patients >50 years of age had more mutations.TET2,SRSF2, andDNMT3Awere more commonly mutated in patients >50 years old compared to patients ≤50 years old. In general, patients >50 years of age also had more mutations in spliceosomal, epigenetic modifier, and RAS gene families. Although there are age-related differences in molecular features among patients with myelodysplasia, most notably in the incidence ofSRSF2mutations, our results suggest that patients ≤50 years old belong to a disease continuum with a distinct pattern of early onset ancestral events.
authors.affiliation: Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, OH, USA.|Department of Genetics and Genome Science, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Cassandra M
authors.initials: CM
authors.lastname: Hirsch
authors.affiliation: Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, OH, USA.
authors.forename: Bartlomiej P
authors.initials: BP
authors.lastname: Przychodzen
authors.affiliation: Department of Quantitative Health Sciences, Cleveland Clinic Lerner Research Institute, OH, USA.
authors.forename: Tomas
authors.initials: T
authors.lastname: Radivoyevitch
authors.affiliation: Leukemia Program, Taussig Cancer Institute, Cleveland Clinic, OH, USA.
authors.forename: Bhumika
authors.initials: B
authors.lastname: Patel
authors.affiliation: Leukemia Program, Taussig Cancer Institute, Cleveland Clinic, OH, USA.
authors.forename: Swapna
authors.initials: S
authors.lastname: Thota
authors.affiliation: Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, OH, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Clemente
authors.affiliation: Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, OH, USA.
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Nagata
authors.affiliation: Department of Genetics and Genome Science, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: LaFramboise
authors.affiliation: Leukemia Program, Taussig Cancer Institute, Cleveland Clinic, OH, USA.
authors.forename: Hetty E
authors.initials: HE
authors.lastname: Carraway
authors.affiliation: Leukemia Program, Taussig Cancer Institute, Cleveland Clinic, OH, USA.
authors.forename: Aziz
authors.initials: A
authors.lastname: Nazha
authors.affiliation: Leukemia Program, Taussig Cancer Institute, Cleveland Clinic, OH, USA.
authors.forename: Mikkael A
authors.initials: MA
authors.lastname: Sekeres
authors.affiliation: Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, OH, USA.|Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Makishima
authors.affiliation: Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, OH, USA maciejj@ccf.org.|Leukemia Program, Taussig Cancer Institute, Cleveland Clinic, OH, USA.
authors.forename: Jaroslaw P
authors.initials: JP
authors.lastname: Maciejewski
mesh_terms: D000328:Adult; D000367:Age Factors; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics; D000090205:DNA Methyltransferase 3A; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics; D049308:Dioxygenases; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009190:Myelodysplastic Syndromes / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D000068103:Serine-Arginine Splicing Factors / Q000235:genetics; D055815:Young Adult
chemical_list: D004268:DNA-Binding Proteins; C000717967:DNMT3A protein, human; D011518:Proto-Oncogene Proteins; C073288:SRSF2 protein, human; D000068103:Serine-Arginine Splicing Factors; D049308:Dioxygenases; C541081:TET2 protein, human; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A