title: Recurrent reciprocal RNA chimera involving YPEL5 and PPP1CB in chronic lymphocytic leukemia.
abstract: Chronic lymphocytic leukemia (CLL) is the most common form of leukemia in adults in the Western hemisphere. Tumor-specific chromosomal translocations, characteristic findings in several human malignancies that directly lead to malignant transformation, have not been identified in CLL. Using paired-end transcriptome sequencing, we identified recurrent and reciprocal RNA chimeras involving yippee like 5 (YPEL5) and serine/threonine-protein phosphatase PP1-beta-catalytic subunit (PPP1CB) in CLL. Two of seven index cases (28%) harbored the reciprocal RNA chimeras in our initial screening. Using quantitative real-time PCR (q real-time PCR), YPEL5/PPP1CB and PPP1CB/YPEL5 fusion transcripts were detected in 97 of 103 CLL samples (95%) but not in paired normal samples, benign lymphocytes, or various unrelated cancers. Whole-genome sequencing and Southern blotting demonstrated no evidence for a genomic fusion between YPEL5 and PPP1CB. YPEL5/PPP1CB chimera, when introduced into mammalian cells, expressed a truncated PPP1CB protein that demonstrated diminished phosphatase activity. PPP1CB silencing resulted in enhanced proliferation and colony formation of MEC1 and JVM3 cells, implying a role in the pathogenesis of mature B-cell leukemia. These studies uncover a potential role for recurrent RNA chimeras involving phosphatases in the pathogenesis of a common form of leukemia.
authors: Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors: Thirunavukkarasu
authors: T
authors: Velusamy
authors: Nallasivam
authors: N
authors: Palanisamy
authors: Shanker
authors: S
authors: Kalyana-Sundaram
authors: Anagh Anant
authors: AA
authors: Sahasrabuddhe
authors: Christopher A
authors: CA
authors: Maher
authors: Daniel R
authors: DR
authors: Robinson
authors: David W
authors: DW
authors: Bahler
authors: Timothy T
authors: TT
authors: Cornell
authors: Thomas E
authors: TE
authors: Wilson
authors: Megan S
authors: MS
authors: Lim
authors: Arul M
authors: AM
authors: Chinnaiyan
authors: Kojo S J
authors: KS
authors: Elenitoba-Johnson
mesh_terms: D015139:Blotting, Southern; D020134:Catalytic Domain; D018797:Cell Cycle Proteins / Q000235:genetics*; D050939:Gene Fusion; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics*; D054645:Protein Phosphatase 1 / Q000235:genetics*; D012334:RNA, Neoplasm / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D018797:Cell Cycle Proteins; D012334:RNA, Neoplasm; C553177:YPEL5 protein, human; C517188:PPP1CB protein, human; D054645:Protein Phosphatase 1
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