title: Fusion of the tumor-suppressor gene CHEK2 and the gene for the regulatory subunit B of protein phosphatase 2 PPP2R2A in childhood teratoma.
abstract: We characterized the molecular genetic consequences of a balanced chromosome translocation t(8;22)(p21;q12), which occurred as the sole cytogenetic aberration in short-term cultured cells from an intrathoracic mature teratoma in a 15-year-old girl. Fluorescence in situ hybridization and reverse transcription-polymerase chain reaction disclosed that t(8;22) resulted in the fusion of the genes PPP2R2A and CHEK2, with an inserted fragment belonging to class I endogenous retrovirus-related sequences at the junction. Sequencing of the two genes did not reveal any additional mutation. None of the three detected PPP2R2A/CHEK2 fusion transcripts resulted in an in-frame PPP2R2A/CHEK2 chimerical open reading frame; however, in all of them, the known open reading frame of CHEK2 was preserved. Thus, promoter swapping leading to deregulated CHEK2 expression would be the most likely oncogenic mechanism. Whereas inactivating mutations of CHEK2 previously have been described in a variety of sporadic tumors and in inherited cancer-predisposing syndromes, PPP2R2A, encoding a regulatory subunit of the multimeric enzyme phosphatase 2, has not been directly implicated in tumorigenesis. Our findings suggest that deregulation of CHEK2 and/or PPP2R2A is of pathogenetic importance in at least a subset of germ cell tumors.
authors.affiliation: Department of Clinical Genetics, Lund University Hospital, 221 85 Lund, Sweden. yuesheng.jin@med.lu.se
authors.forename: Yuesheng
authors.initials: Y
authors.lastname: Jin
authors.forename: Fredrik
authors.initials: F
authors.lastname: Mertens
authors.forename: Carl-Magnus
authors.initials: CM
authors.lastname: Kullendorff
authors.forename: Ioannis
authors.initials: I
authors.lastname: Panagopoulos
mesh_terms: D000293:Adolescent; D000595:Amino Acid Sequence; D001483:Base Sequence; D064447:Checkpoint Kinase 2; D002869:Chromosome Aberrations; D002892:Chromosomes, Human, Pair 22; D002898:Chromosomes, Human, Pair 8; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008969:Molecular Sequence Data; D009373:Neoplasms, Germ Cell and Embryonal / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D010749:Phosphoprotein Phosphatases / Q000235:genetics* / Q000502:physiology; D011401:Promoter Regions, Genetic; D054648:Protein Phosphatase 2; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000502:physiology; D013724:Teratoma / Q000201:enzymology* / Q000235:genetics; D014178:Translocation, Genetic
chemical_list: D015514:Oncogene Proteins, Fusion; C512974:PPP2R2A protein, human; D064447:Checkpoint Kinase 2; C578634:CHEK2 protein, human; D017346:Protein Serine-Threonine Kinases; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2