title: Mutational Landscape and Gene Expression Patterns in Adult Acute Myeloid Leukemias with Monosomy 7 as a Sole Abnormality.
abstract: Monosomy of chromosome 7 is the most frequent autosomal monosomy in acute myeloid leukemia (AML), where it associates with poor clinical outcomes. However, molecular features associated with this sole monosomy subtype (-7 AML), which may give insights into the basis for its poor prognosis, have not been characterized. In this study, we analyzed 36 cases of -7 AML for mutations in 81 leukemia/cancer-associated genes using a customized targeted next-generation sequencing panel (Miseq). Global gene and miRNA expression profiles were also determined using paired RNA and small RNA sequencing data. Notably, gene mutations were detected in all the major AML-associated functional groups, which include activated signaling, chromatin remodeling, cohesin complex, methylation, NPM1, spliceosome, transcription factors, and tumor suppressors. Gene mutations in the chromatin remodeling groups were relatively more frequent in patients <60 years of age, who also had less mutations in the methylation and spliceosome groups compared with patients ≥60 years of age. Novel recurrent mutational events in AML were identified in the SMARCA2 gene. In patients ≥60 years of age, the presence of spliceosome mutations associated with a lower complete remission rate (P = 0.03). RNA sequencing revealed distinct gene and miRNA expression patterns between the sole -7 and non -7 AML cases, with reduced expression, as expected, of many genes and miRNAs mapped to chromosome 7, and overexpression of ID1, MECOM, and PTPRM, among others. Overall, our findings illuminate a number of molecular features of the underlying aggressive pathobiology in -7 AML patients. Cancer Res; 77(1); 207-18. ©2016 AACR.
authors: The Ohio State University Comprehensive Cancer Center, Columbus, Ohio. ann-kathrin.eisfeld@osumc.edu clara.bloomfield@osumc.edu.
authors: Ann-Kathrin
authors: AK
authors: Eisfeld
authors: The Ohio State University Comprehensive Cancer Center, Columbus, Ohio.|Alliance Statistics and Data Center, Mayo Clinic, Rochester, Minnesota.
authors: Jessica
authors: J
authors: Kohlschmidt
authors: The Ohio State University Comprehensive Cancer Center, Columbus, Ohio.
authors: Krzysztof
authors: K
authors: Mrózek
authors: Department of Morphology, Surgery, and Experimental Medicine, University of Ferrara, Ferrara, Italy.
authors: Stefano
authors: S
authors: Volinia
authors: Division of Hematology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio.
authors: James S
authors: JS
authors: Blachly
authors: The Ohio State University Comprehensive Cancer Center, Columbus, Ohio.|Alliance Statistics and Data Center, Mayo Clinic, Rochester, Minnesota.
authors: Deedra
authors: D
authors: Nicolet
authors: Division of Hematology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio.
authors: Christopher
authors: C
authors: Oakes
authors: Division of Hematology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio.
authors: Karl
authors: K
authors: Kroll
authors: Division of Hematology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio.
authors: Shelley
authors: S
authors: Orwick
authors: University of Alabama at Birmingham, Birmingham, Alabama.
authors: Andrew J
authors: AJ
authors: Carroll
authors: Dana-Farber/Partners CancerCare, Boston, Massachusetts.
authors: Richard M
authors: RM
authors: Stone
authors: Division of Hematology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio.
authors: John C
authors: JC
authors: Byrd
authors: The Ohio State University Comprehensive Cancer Center, Columbus, Ohio.
authors: Albert
authors: A
authors: de la Chapelle
authors: The Ohio State University Comprehensive Cancer Center, Columbus, Ohio. ann-kathrin.eisfeld@osumc.edu clara.bloomfield@osumc.edu.
authors: Clara D
authors: CD
authors: Bloomfield
mesh_terms: D000328:Adult; D000368:Aged; D002872:Chromosome Deletion; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D020869:Gene Expression Profiling; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D053208:Kaplan-Meier Estimate; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D000090243:Nucleophosmin; D016016:Proportional Hazards Models; D059467:Transcriptome