Recurrent rearrangement of the PHF1 gene in ossifying fibromyxoid tumors.
Ossifying fibromyxoid tumor (OFMT) is a soft tissue tumor of unknown lineage. Although most cases are histologically and clinically benign, some show malignant morphological features and local recurrences are not uncommon; a few may even metastasize. In the present study, cytogenetic analysis identified different structural rearrangements of chromosome band 6p21 in tumor cells from three cases of OFMT, including one with typical, one with atypical, and one with malignant morphological features. Mapping of the 6p21 breakpoint by fluorescence in situ hybridization (FISH) indicated that the PHF1 gene was rearranged in all three cases. Further FISH, 5'-rapid amplification of cDNA ends, and RT-PCR analyses disclosed an EP400/PHF1 fusion transcript in one of the cases. Interphase FISH on tumor sections from 13 additional cases of OFMT showed rearrangement of the PHF1 locus in four of four typical, two of three atypical, and one of six malignant lesions. Thus, the PHF1 gene, previously shown to be the 3'-partner of fusion genes in endometrial stromal tumors, is also recurrently involved in the pathogenesis of OFMTs, irrespective of whether they are diagnosed as typical, atypical, or malignant lesions. The PHF1 protein interacts with the polycomb-repressive complex 2 (PRC2), which, in turn, regulates the expression of a variety of developmental genes. Thus, the results indicate that deregulation of PRC2 target genes is crucial for OFMT development.
Department of Clinical Genetics, University and Regional Laboratories, Lund University, Sweden. samuel.gebre-medhin@med.lu.se
Samuel
S
Gebre-Medhin
Karolin H
KH
Nord
Emely
E
Möller
Nils
N
Mandahl
Linda
L
Magnusson
Jenny
J
Nilsson
Vickie Y
VY
Jo
Fredrik
F
Vult von Steyern
Otte
O
Brosjö
Olle
O
Larsson
Henryk A
HA
Domanski
Raf
R
Sciot
Maria
M
Debiec-Rychter
Christopher D M
CD
Fletcher
Fredrik
F
Mertens
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D001859:Bone Neoplasms / Q000235:genetics* / Q000473:pathology; D048430:Cell Shape; D019457:Chromosome Breakage; D002877:Chromosomes, Human / Q000235:genetics; D020732:Cytogenetic Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D018214:Fibroma, Ossifying / Q000235:genetics* / Q000473:pathology; D015321:Gene Rearrangement / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008677:Metaphase; D008875:Middle Aged; D008969:Molecular Sequence Data; D016612:Paraffin Embedding; D063146:Polycomb-Group Proteins; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012008:Recurrence; D014157:Transcription Factors / Q000235:genetics*
D004268:DNA-Binding Proteins; C112309:PHF1 protein, human; D063146:Polycomb-Group Proteins; D014157:Transcription Factors