title: Novel fusion of MYST/Esa1-associated factor 6 and PHF1 in endometrial stromal sarcoma.
abstract: Rearrangement of chromosome band 6p21 is recurrent in endometrial stromal sarcoma (ESS) and targets the PHF1 gene. So far, PHF1 was found to be the 3' partner in the JAZF1-PHF1 and EPC1-PHF1 chimeras but since the 6p21 rearrangements involve also other chromosomal translocation partners, other PHF1-fusions seem likely. Here, we show that PHF1 is recombined with a novel fusion partner, MEAF6 from 1p34, in an ESS carrying a t(1;6)(p34;p21) translocation as the sole karyotypic anomaly. 5'-RACE, RT-PCR, and sequencing showed the presence of an MEAF6-PHF1 chimera in the tumor with exon 5 of MEAF6 being fused in-frame to exon 2 of PHF1 so that the entire PHF1 coding region becomes the 3' terminal part of the MEAF6-PHF1 fusion. The predicted fusion protein is composed of 750 amino acids and contains the histone acetyltransferase subunit NuA4 domain of MEAF6 and the tudor, PHD zinc finger, and MTF2 domains of PHF1. Although the specific functions of the MEAF6 and PHF1 proteins and why they are targeted by a neoplasia-specific gene fusion are not directly apparent, it seems that rearrangement of genes involved in acetylation (EPC1, MEAF6) and methylation (PHF1), resulting in aberrant gene expression, is a common theme in ESS pathogenesis.
authors: Section for Cancer Cytogenetics, Institute for Medical Informatics, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway. ioannis.panagopoulos@rr-research.no
authors: Ioannis
authors: I
authors: Panagopoulos
authors: Francesca
authors: F
authors: Micci
authors: Jim
authors: J
authors: Thorsen
authors: Ludmila
authors: L
authors: Gorunova
authors: Anne Mette
authors: AM
authors: Eibak
authors: Bodil
authors: B
authors: Bjerkehagen
authors: Ben
authors: B
authors: Davidson
authors: Sverre
authors: S
authors: Heim
mesh_terms: D000328:Adult; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000601:surgery; D005260:Female; D051548:Histone Acetyltransferases / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D050596:Oncogene Fusion; D015514:Oncogene Proteins, Fusion / Q000235:genetics* / Q000378:metabolism; D063146:Polycomb-Group Proteins; D018203:Sarcoma, Endometrial Stromal / Q000235:genetics* / Q000378:metabolism / Q000601:surgery; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D015514:Oncogene Proteins, Fusion; C112309:PHF1 protein, human; D063146:Polycomb-Group Proteins; D014157:Transcription Factors; D051548:Histone Acetyltransferases