Fusion of the AHRR and NCOA2 genes through a recurrent translocation t(5;8)(p15;q13) in soft tissue angiofibroma results in upregulation of aryl hydrocarbon receptor target genes.

Summary, in English

Soft tissue angiofibroma is a recently delineated tumor type of unknown cellular origin. Cytogenetic analysis of four cases showed that they shared a t(5;8)(p15;q13). In three of them it was the sole change, underlining its pathogenetic significance. FISH mapping suggested the involvement of the aryl hydrocarbon receptor repressor (AHRR) and nuclear receptor coactivator 2 (NCOA2) genes in 5p15 and 8q13, respectively. RT-PCR revealed in-frame AHRR/NCOA2 and NCOA2/AHHR transcripts in all four cases. Interphase FISH on paraffin-embedded tissue from 10 further cases without cytogenetic data showed that three were positive for fusion of AHRR and NCOA2. While AHRR has never been implicated in gene fusions before, NCOA2 is the 3'-partner in fusions with MYST3 and ETV6 in leukemias and with PAX3 and HEY1 in sarcomas. As in the previously described fusion proteins, NCOA2 contributes with its two activation domains to the AHRR/NCOA2 chimera, substituting for the repressor domain of AHRR. Because the amino terminal part of the transcription factor AHRR, responsible for the recognition of xenobiotic response elements in target genes and for heterodimerization, shows extensive homology with the aryl hydrocarbon receptor (AHR), the fusion is predicted to upregulate the AHR/ARNT signaling pathway. Indeed, global gene expression analysis showed upregulation of CYP1A1 as well as other typical target genes of this pathway, such as those encoding toll-like receptors. Apart from providing a diagnostic marker for soft tissue angiofibroma, the results also suggest that this tumor constitutes an interesting model for evaluating the cellular effects of AHR signaling. © 2012 Wiley Periodicals, Inc.

• Författare: Yuesheng Jin; Emely Möller; Karolin Hansén Nord; Nils Mandahl; Fredrik Vult von Steyern; Henryk Domanski; Adrian Mariño-Enríquez; Linda Magnusson; Jenny Nilsson; Raf Sciot; Christopher D M Fletcher; Maria Debiec-Rychter; Fredrik Mertens
• Avdelning/ar: Avdelningen för klinisk genetik; Ortopedi, Lund; Tumörmikromiljö; BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
• Publiceringsår: 2012
• Språk: Engelska
• Sidor: 510-520
• Publikation/Tidskrift/Serie: Genes, Chromosomes and Cancer
• Volym: 51
• Issue: 5
• Länkar: http://www.ncbi.nlm.nih.gov/pubmed/22337624?dopt=Abstract; http://dx.doi.org/10.1002/gcc.21939
• Dokumenttyp: Artikel i tidskrift
• Förlag: John Wiley & Sons Inc.
• Ämne: Medical Genetics; Cancer and Oncology
• Status: Published
• ISBN/ISSN/Övrigt: ISSN: 1045-2257