No gene copy number changes in Dupuytren's contracture by array comparative genomic hybridization

Department of Pathology, Haartman Institute and HUSLAB, University of Helsinki and University Central Hospital, POB 21 (Haartmaninkatu 3), Helsinki 00014, Finland.
Cancer genetics and cytogenetics (Impact Factor: 1.93). 06/2008; 183(1):6-8. DOI: 10.1016/j.cancergencyto.2008.01.018
Source: PubMed


Dupuytren's contracture (DC), a benign disease of unknown origin, is characterized by abnormal fibroblast proliferation and matrix deposition within the palmar and plantar faciae, causing contracture of the digits. Conventional cytogenetic studies of cultured fibroblast cells from DC nodules have revealed nonrecurrent, but usually normal, clonal (mainly +7, +8, and -Y, plus structural changes) and sporadic (nonclonal) numerical/structural rearrangements. No unique cytogenetic features of DC are known so far. We used 44K oligonucleotide-based array comparative genomic hybridization to obtain a wide pattern of chromosomal imbalances in 18 patients with DC. The genome-wide analysis revealed no changes of DNA copy number sequences. Accordingly, gene amplifications or deletions are apparently not involved in the progression of abnormal fibroblast proliferation and matrix deposition that lead to DC.

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Available from: Marcelo Larramendy, Oct 24, 2015
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    • "We take the approach of comparing primary fibroblasts derived from surgically resected DD contracture (cord) tissue (DD cells) to fibroblasts derived from the palmar fascia of the adjacent, phenotypically unaffected digit exposed during surgery (PF cells). While DD may be associated with increased cancer mortality in some populations [11] [12], patients with a family history of finger contractures do not display any major chromosomal rearrangements or deletions [13] and DD is considered a benign, heritable fibrosis [4]. Single nucleotide polymorphisms (SNPs) have been identified as potential markers of this heritability [14], and these polymorphisms are predicted to be present in all somatic tissues in these patients rather than limited to Biochimica et Biophysica Acta 1832 (2013) 1511–1519 ☆ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. "
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    ABSTRACT: Dupuytren's Disease (DD) is a common and heritable fibrosis of the palmar fascia that typically manifests as permanent finger contractures. The molecular interactions that induce the development of hyper-contractile fibroblasts, or myofibroblasts, in DD are poorly understood. We have identified IGF2 and IGFBP6, encoding insulin-like growth factor (IGF)-II and IGF binding protein (IGFBP)-6 respectively, as reciprocally dysregulated genes and proteins in primary cells derived from contracture tissues (DD cells). Recombinant IGFBP-6 inhibited the proliferation of DD cells, patient-matched controls (PF) cells and normal palmar fascia (CT) cells. Co-treatments with IGF-II, a high affinity IGFBP-6 ligand, were unable to rescue these effects. A non-IGF-II binding analog of IGFBP-6 also inhibited cellular proliferation, implicating IGF-II-independent roles for IGFBP-6 in this process. IGF-II enhanced the proliferation of CT cells, but not DD or PF cells, and significantly enhanced DD and PF cell contractility in stressed collagen lattices. While IGFBP-6 treatment did not affect cellular contractility, it abrogated the IGF-II-induced contractility of DD and PF cells in stressed collagen lattices. IGF-II also significantly increased the contraction of DD cells in relaxed lattices, however this effect was not evident in relaxed collagen lattices containing PF cells. The disparate effects of IGF-II on DD and PF cells in relaxed and stressed contraction models suggest that IGF-II can enhance lattice contractility through more than one mechanism. This is the first report to implicate IGFBP-6 as a suppressor of cellular proliferation and IGF-II as an inducer of cellular contractility in this connective tissue disease.
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