Recurrent Rearrangement of the PHF1 Gene in Ossifying Fibromyxoid Tumors.

Summary, in English

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.

• Author: Samuel Gebre-Medhin; Karolin Hansén Nord; Emely Möller; Nils Mandahl; Linda Magnusson; Jenny Nilsson; Vickie Y Jo; Fredrik Vult von Steyern; Otte Brosjö; Olle Larsson; Henryk Domanski; Raf Sciot; Maria Debiec-Rychter; Christopher D M Fletcher; Fredrik Mertens
• Department/s: Division of Clinical Genetics; Orthopaedics (Lund); Tumor microenvironment; BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
• Publishing year: 2012
• Language: English
• Pages: 1069-1077
• Publication/Series: American Journal of Pathology
• Volume: 181
• Issue: 3
• Links: http://www.ncbi.nlm.nih.gov/pubmed/22796436?dopt=Abstract; http://dx.doi.org/10.1016/j.ajpath.2012.05.030
• Document type: Journal article
• Publisher: American Society for Investigative Pathology
• Topic: Cell and Molecular Biology
• Status: Published
• ISBN/ISSN/Other: ISSN: 1525-2191