title: Mutational profiling of therapy-related myelodysplastic syndromes and acute myeloid leukemia by next generation sequencing, a comparison with de novo diseases.
abstract: In this study we used a next generation sequencing-based approach to profile gene mutations in therapy-related myelodysplastic syndromes (t-MDS) and acute myeloid leukemia (t-AML); and compared these findings with de novo MDS/AML. Consecutive bone marrow samples of 498 patients, including 70 therapy-related (28 MDS and 42 AML) and 428 de novo (147 MDS and 281 AML) were analyzed using a modified-TruSeq Amplicon Cancer Panel (Illumina) covering mutation hotspots of 53 genes. Overall, mutation(s) were detected in 58.6% of t-MDS/AML and 56.8% of de novo MDS/AML. Of therapy-related cases, mutations were detected in 71.4% of t-AML versus 39.3% t-MDS (p=0.0127). TP53 was the most common mutated gene in t-MDS (35.7%) as well as t-AML (33.3%), significantly higher than de novo MDS (17.7%) (p=0.0410) and de novo AML (12.8%) (p=0.0020). t-AML showed more frequent PTPN11 but less NPM1 and FLT3 mutations than de novo AML. In summary, t-MDS/AML shows a mutation profile different from their de novo counterparts. TP53 mutations are highly and similarly prevalent in t-MDS and t-AML but mutations in genes other than TP53 were more frequent in t-AML than t-MDS. The molecular genetic profiling further expands our understanding in this group of clinically aggressive yet heterogeneous myeloid neoplasms.
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Chi Young
authors.initials: CY
authors.lastname: Ok
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Keyur P
authors.initials: KP
authors.lastname: Patel
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Garcia-Manero
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Routbort
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Hematology, Central South University Xiangya Hospital, Changsha, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Fu
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Guilin
authors.initials: G
authors.lastname: Tang
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Maitrayee
authors.initials: M
authors.lastname: Goswami
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Singh
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Rashmi
authors.initials: R
authors.lastname: Kanagal-Shamanna
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Sherry A
authors.initials: SA
authors.lastname: Pierce
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Ken H
authors.initials: KH
authors.lastname: Young
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Hagop M
authors.initials: HM
authors.lastname: Kantarjian
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: L Jeffrey
authors.initials: LJ
authors.lastname: Medeiros
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Rajyalakshmi
authors.initials: R
authors.lastname: Luthra
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address: swang5@mdanderson.org.
authors.forename: Sa A
authors.initials: SA
authors.lastname: Wang
mesh_terms: D015331:Cohort Studies; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D009190:Myelodysplastic Syndromes / Q000175:diagnosis / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D016609:Neoplasms, Second Primary / Q000175:diagnosis / Q000235:genetics*; D000090243:Nucleophosmin; D011379:Prognosis
chemical_list: C000716967:NPM1 protein, human; D009363:Neoplasm Proteins; D000090243:Nucleophosmin
keywords: AML; Karyotype; MDS; Next generation sequencing; TP53; Therapy-related