title: Integrated genomic DNA/RNA profiling of hematologic malignancies in the clinical setting.
abstract: The spectrum of somatic alterations in hematologic malignancies includes substitutions, insertions/deletions (indels), copy number alterations (CNAs), and a wide range of gene fusions; no current clinically available single assay captures the different types of alterations. We developed a novel next-generation sequencing-based assay to identify all classes of genomic alterations using archived formalin-fixed paraffin-embedded blood and bone marrow samples with high accuracy in a clinically relevant time frame, which is performed in our Clinical Laboratory Improvement Amendments-certified College of American Pathologists-accredited laboratory. Targeted capture of DNA/RNA and next-generation sequencing reliably identifies substitutions, indels, CNAs, and gene fusions, with similar accuracy to lower-throughput assays that focus on specific genes and types of genomic alterations. Profiling of 3696 samples identified recurrent somatic alterations that impact diagnosis, prognosis, and therapy selection. This comprehensive genomic profiling approach has proved effective in detecting all types of genomic alterations, including fusion transcripts, which increases the ability to identify clinically relevant genomic alterations with therapeutic relevance.
authors.affiliation: Foundation Medicine, Cambridge, MA;
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authors.affiliation: Leukemia Service, Department of Medicine, Human Oncology and Pathogenesis Program.
authors.forename: Omar
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authors.lastname: Abdel-Wahab
authors.affiliation: Foundation Medicine, Cambridge, MA;
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authors.initials: MK
authors.lastname: Nahas
authors.affiliation: Foundation Medicine, Cambridge, MA;
authors.forename: Kai
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authors.lastname: Wang
authors.affiliation: Leukemia Service, Department of Medicine, Human Oncology and Pathogenesis Program.
authors.forename: Raajit K
authors.initials: RK
authors.lastname: Rampal
authors.affiliation: Cancer Biology and Genetics Program, Lymphoma Service, Department of Medicine.
authors.forename: Andrew M
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authors.lastname: Intlekofer
authors.affiliation: Human Oncology and Pathogenesis Program.
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authors.affiliation: Cancer Biology and Genetics Program, Leukemia Center, Department of Pediatrics, and.
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authors.affiliation: Foundation Medicine, Cambridge, MA;
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authors.lastname: Frampton
authors.affiliation: Foundation Medicine, Cambridge, MA;
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authors.initials: LE
authors.lastname: Young
authors.affiliation: Foundation Medicine, Cambridge, MA;
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authors.lastname: Zhong
authors.affiliation: Foundation Medicine, Cambridge, MA;
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authors.lastname: Bailey
authors.affiliation: Foundation Medicine, Cambridge, MA;
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authors.initials: JR
authors.lastname: White
authors.affiliation: Foundation Medicine, Cambridge, MA;
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authors.lastname: Roels
authors.affiliation: Foundation Medicine, Cambridge, MA;
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authors.initials: J
authors.lastname: Deffenbaugh
authors.affiliation: Foundation Medicine, Cambridge, MA;
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authors.affiliation: Foundation Medicine, Cambridge, MA;
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authors.lastname: Brennan
authors.affiliation: Foundation Medicine, Cambridge, MA;
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authors.lastname: Rosenzweig
authors.affiliation: Foundation Medicine, Cambridge, MA;
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authors.forename: Kristina M
authors.initials: KM
authors.lastname: Knapp
authors.affiliation: Foundation Medicine, Cambridge, MA;
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authors.initials: KW
authors.lastname: Brennan
authors.affiliation: Foundation Medicine, Cambridge, MA;
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authors.initials: AL
authors.lastname: Donahue
authors.affiliation: Foundation Medicine, Cambridge, MA;
authors.forename: Geneva
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authors.affiliation: Foundation Medicine, Cambridge, MA;
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authors.lastname: Garcia
authors.affiliation: Foundation Medicine, Cambridge, MA;
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authors.initials: ST
authors.lastname: Beckstrom
authors.affiliation: Foundation Medicine, Cambridge, MA;
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authors.lastname: Zhao
authors.affiliation: Foundation Medicine, Cambridge, MA;
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authors.initials: E
authors.lastname: White
authors.affiliation: Foundation Medicine, Cambridge, MA;
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authors.initials: V
authors.lastname: Banning
authors.affiliation: Foundation Medicine, Cambridge, MA;
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authors.initials: J
authors.lastname: Buell
authors.affiliation: Foundation Medicine, Cambridge, MA;
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authors.affiliation: Foundation Medicine, Cambridge, MA;
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authors.initials: JS
authors.lastname: Ross
authors.affiliation: Foundation Medicine, Cambridge, MA;
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authors.initials: D
authors.lastname: Morosini
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authors.forename: Anas
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authors.affiliation: Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY;
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authors.affiliation: Department of Medicine (Oncology), Albert Einstein College of Medicine, Yeshiva University, New York, NY;
authors.forename: Elisabeth
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authors.lastname: Paietta
authors.affiliation: Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN;
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authors.lastname: Roberts
authors.affiliation: Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN;
authors.forename: Charles
authors.initials: C
authors.lastname: Mullighan
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY;
authors.forename: Ahmet
authors.initials: A
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authors.affiliation: Cancer Biology and Genetics Program, Leukemia Center, Department of Pediatrics, and.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Armstrong
authors.affiliation: Foundation Medicine, Cambridge, MA; Division of Hematology and Oncology, Tufts University Medical Center, Boston, MA; and.
authors.forename: Tariq
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authors.lastname: Mughal
authors.affiliation: Foundation Medicine, Cambridge, MA;
authors.forename: Jo-Anne
authors.initials: JA
authors.lastname: Vergilio
authors.affiliation: Foundation Medicine, Cambridge, MA;
authors.forename: Elaine
authors.initials: E
authors.lastname: Labrecque
authors.affiliation: Foundation Medicine, Cambridge, MA;
authors.forename: Rachel
authors.initials: R
authors.lastname: Erlich
authors.affiliation: Foundation Medicine, Cambridge, MA;
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authors.lastname: Vietz
authors.affiliation: Foundation Medicine, Cambridge, MA;
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authors.initials: R
authors.lastname: Yelensky
authors.affiliation: Foundation Medicine, Cambridge, MA;
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authors.affiliation: Foundation Medicine, Cambridge, MA;
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authors.initials: VA
authors.lastname: Miller
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authors.forename: Marcel R M
authors.initials: MR
authors.lastname: van den Brink
authors.affiliation: Foundation Medicine, Cambridge, MA;
authors.forename: Geoff A
authors.initials: GA
authors.lastname: Otto
authors.affiliation: Foundation Medicine, Cambridge, MA;
authors.forename: Doron
authors.initials: D
authors.lastname: Lipson
authors.affiliation: Leukemia Service, Department of Medicine, Human Oncology and Pathogenesis Program, Leukemia Center.
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authors.initials: RL
authors.lastname: Levine
mesh_terms: D002869:Chromosome Aberrations; D019411:Clinical Laboratory Techniques / Q000379:methods; D016172:DNA Fingerprinting / Q000379:methods*; D004252:DNA Mutational Analysis / Q000379:methods; D004273:DNA, Neoplasm / Q000032:analysis; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic; D023281:Genomics / Q000379:methods*; D019337:Hematologic Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D009154:Mutation; D011110:Polymorphism, Genetic; D012334:RNA, Neoplasm / Q000032:analysis; D012680:Sensitivity and Specificity; D018511:Systems Integration
chemical_list: D004273:DNA, Neoplasm; D012334:RNA, Neoplasm