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Multicentric dermatofibrosarcoma protuberans in patients with adenosine deaminase-deficient severe combined immune deficiency.
MedLine Citation:
PMID:  22153773     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is a rare malignant skin tumor associated with a characteristic chromosomal translocation (t[17;22][q22;q13]) resulting in the COL1A1-platelet-derived growth factor β(PDGFB) fusion gene. This malignancy is rarely diagnosed in childhood. OBJECTIVE: We observed a high incidence of this tumor in children affected with adenosine deaminase-deficient severe combined immunodeficiency (ADA-SCID). METHODS: Twelve patients with ADA-SCID were evaluated with a complete dermatologic examination and skin biopsy when indicated. Conventional cytogenetic and molecular analyses (fluorescence in situ hybridization, RT-PCR, or both) were performed when possible. RESULTS: Eight patients were found to have DFSP. Six patients had multicentric involvement (4-15 lesions), primarily of the trunk and extremities. Most lesions presented as 2- to 15-mm, round atrophic plaques. Nodular lesions were present in 3 patients. In all cases CD34 expression was diffusely positive, and diagnosis was confirmed either by means of cytogenetic analysis, molecular testing, or both. The characteristic DFSP-associated translocation, t(17;22)(q22;q13), was identified in 6 patients; results of fluorescence in situ hybridization were positive for fusion of the COL1A1 and PDGFB loci in 7 patients; and RT-PCR showed the COL1A1-PDGFB fusion transcript in 6 patients. CONCLUSIONS: We describe a previously unrecognized association between ADA-SCID and DFSP with unique features, such as multicentricity and occurrence in early age. We hypothesize that the t(17;22)(q22;q13) translocation that results in dermal overexpression of PDGFB and favors the development of fibrotic tumors might arise because of the known DNA repair defect in patients with ADA-SCID. Although the natural course of DFSP in the setting of ADA-SCID is unknown, this observation should prompt regular screening for DFSP in patients with ADA-SCID.
Authors:
Chimene Kesserwan; Robert Sokolic; Edward W Cowen; Elizabeth Garabedian; Kerstin Heselmeyer-Haddad; Chyi-Chia Richard Lee; Stefania Pittaluga; Clarymar Ortiz; Kristin Baird; Dolores Lopez-Terrada; Julia Bridge; Alan S Wayne; Fabio Candotti
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-12-6
Journal Detail:
Title:  The Journal of allergy and clinical immunology     Volume:  -     ISSN:  1097-6825     ISO Abbreviation:  -     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-12-13     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1275002     Medline TA:  J Allergy Clin Immunol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.
Affiliation:
Genetics and Molecular Biology Branch and the Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Md.
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