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Recurrent Rearrangement of the PHF1 Gene in Ossifying Fibromyxoid Tumors.

Gebre-Medhin, Samuel LU ; Hansén Nord, Karolin LU ; Möller, Emely LU ; Mandahl, Nils LU ; Magnusson, Linda LU ; Nilsson, Jenny LU ; Jo, Vickie Y; Vult von Steyern, Fredrik LU ; Brosjö, Otte and Larsson, Olle, et al. (2012) In American Journal of Pathology 181(3). p.1069-1077
Abstract
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... (More)
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. (Less)
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American Journal of Pathology
volume
181
issue
3
pages
1069 - 1077
publisher
American Society for Investigative Pathology
external identifiers
  • wos:000309251100033
  • pmid:22796436
  • scopus:84865268959
ISSN
1525-2191
DOI
10.1016/j.ajpath.2012.05.030
language
English
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yes
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f41e86b0-c51c-412d-b4f3-32114dd72d36 (old id 2967138)
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http://www.ncbi.nlm.nih.gov/pubmed/22796436?dopt=Abstract
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2012-08-09 18:25:43
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2017-11-05 04:43:49
@article{f41e86b0-c51c-412d-b4f3-32114dd72d36,
  abstract     = {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       = {Gebre-Medhin, Samuel and Hansén Nord, Karolin and Möller, Emely and Mandahl, Nils and Magnusson, Linda and Nilsson, Jenny and Jo, Vickie Y and Vult von Steyern, Fredrik and Brosjö, Otte and Larsson, Olle and Domanski, Henryk and Sciot, Raf and Debiec-Rychter, Maria and Fletcher, Christopher D M and Mertens, Fredrik},
  issn         = {1525-2191},
  language     = {eng},
  number       = {3},
  pages        = {1069--1077},
  publisher    = {American Society for Investigative Pathology},
  series       = {American Journal of Pathology},
  title        = {Recurrent Rearrangement of the PHF1 Gene in Ossifying Fibromyxoid Tumors.},
  url          = {http://dx.doi.org/10.1016/j.ajpath.2012.05.030},
  volume       = {181},
  year         = {2012},
}