title: RT-PCR diagnosis of patients with acute nonlymphocytic leukemia and inv(16)(p13q22) and identification of new alternative splicing in CBFB-MYH11 transcripts.
abstract: As acute nonlymphocytic leukemia (ANLL) with inv(16) (p13q22) or t(16;16)(p13;q22) has been shown to result from the fusion of transcription factor subunit core binding factor (CBFB) to a myosin heavy chain (MYH11), we sought to design methods to detect this rearrangement using reverse transcriptase-polymerase chain reaction (RT-PCR). In all of 27 inv(16)(p13q22) and four t(16;16)(p13;q22) cases tested, a chimeric CBFB-MYH11 transcript coding for an in-frame fusion protein was detected. In a more extensive RT-PCR analysis with different primer pairs, we detected a second new chimeric CBFB-MYH11 transcript in 10 of 11 patients tested. The CBFB-MYH11 reading frame of the second transcript was maintained in one patient but not in the others. We show that the different CBFB-MYH11 transcripts in one patient arise from alternative splicing. Translation of the transcript in which the CBFB-MYH11 reading frame is not maintained leads to a slightly truncated CBFB protein.
authors.affiliation: Department of Human Genetics, Leiden University, Sylvius Laboratories, The Netherlands.
authors.forename: B A
authors.initials: BA
authors.lastname: van der Reijden
authors.forename: M
authors.initials: M
authors.lastname: Lombardo
authors.forename: H G
authors.initials: HG
authors.lastname: Dauwerse
authors.forename: R H
authors.initials: RH
authors.lastname: Giles
authors.forename: D
authors.initials: D
authors.lastname: Mühlematter
authors.forename: M J
authors.initials: MJ
authors.lastname: Bellomo
authors.forename: H W
authors.initials: HW
authors.lastname: Wessels
authors.forename: G C
authors.initials: GC
authors.lastname: Beverstock
authors.forename: G J
authors.initials: GJ
authors.lastname: van Ommen
authors.forename: A
authors.initials: A
authors.lastname: Hagemeijer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001483:Base Sequence; D002648:Child; D007446:Chromosome Inversion; D002885:Chromosomes, Human, Pair 16 / Q000648:ultrastructure*; D050660:Core Binding Factors; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009218:Myosins / Q000096:biosynthesis / Q000235:genetics*; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion / Q000096:biosynthesis / Q000235:genetics*; D016133:Polymerase Chain Reaction; D014176:Protein Biosynthesis; D012326:RNA Splicing; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D050660:Core Binding Factors; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; D014157:Transcription Factors; D009218:Myosins