title: Identification of recurring tumor-specific somatic mutations in acute myeloid leukemia by transcriptome sequencing.
abstract: Genetic lesions are crucial for cancer initiation. Recently, whole genome sequencing, using next generation technology, was used as a systematic approach to identify mutations in genomes of various types of tumors including melanoma, lung and breast cancer, as well as acute myeloid leukemia (AML). Here, we identify tumor-specific somatic mutations by sequencing transcriptionally active genes. Mutations were detected by comparing the transcriptome sequence of an AML sample with the corresponding remission sample. Using this approach, we found five non-synonymous mutations specific to the tumor sample. They include a nonsense mutation affecting the RUNX1 gene, which is a known mutational target in AML, and a missense mutation in the putative tumor suppressor gene TLE4, which encodes a RUNX1 interacting protein. Another missense mutation was identified in SHKBP1, which acts downstream of FLT3, a receptor tyrosine kinase mutated in about 30% of AML cases. The frequency of mutations in TLE4 and SHKBP1 in 95 cytogenetically normal AML patients was 2%. Our study demonstrates that whole transcriptome sequencing leads to the rapid detection of recurring point mutations in the coding regions of genes relevant to malignant transformation.
authors.affiliation: Helmholtz Zentrum München, German Research Center for Environmental Health, Munich, Germany.
authors.forename: P A
authors.initials: PA
authors.lastname: Greif
authors.forename: S H
authors.initials: SH
authors.lastname: Eck
authors.forename: N P
authors.initials: NP
authors.lastname: Konstandin
authors.forename: A
authors.initials: A
authors.lastname: Benet-Pagès
authors.forename: B
authors.initials: B
authors.lastname: Ksienzyk
authors.forename: A
authors.initials: A
authors.lastname: Dufour
authors.forename: A T
authors.initials: AT
authors.lastname: Vetter
authors.forename: H D
authors.initials: HD
authors.lastname: Popp
authors.forename: B
authors.initials: B
authors.lastname: Lorenz-Depiereux
authors.forename: T
authors.initials: T
authors.lastname: Meitinger
authors.forename: S K
authors.initials: SK
authors.lastname: Bohlander
authors.forename: T M
authors.initials: TM
authors.lastname: Strom
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D001853:Bone Marrow / Q000378:metabolism; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017423:Sequence Analysis, RNA
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger