The goal of this Core is to provide DNA, RNA, protein and tissue samples, as well as lymphoblasts, from vascular anomaly patients. In addition, this Core will isolate endothelial cells and non-endothelial cells (mural cells) from hemangiomas and venous anomalies. These samples and cell lines will be used in the analyses related to all three projects of this Program Project. In addition, the Core collects clinical information and pedigree data pertinent to the samples. This data is essential not only for the genetic approaches (Projects 1 and 3), but also when analysing tissues or cell lines for differential expression, somatic mutations or altered behaviour in cell culture in vascular anomaly subtypes (Projects 1, 2, and 3). The sample collection will also ultimately serve for fast and efficient screening of newly identified candidate genes in a well-characterized sample set. The work of Core C is largely based on the extensive collaborative work and expertise of Dr J.B. Mulliken, Vascular Anomalies Center, Boston and Dr LM Boon, Vascular Anomalies Center, Brussels. This collaboration has led to numerous clinical publications describing novel diagnostic measures, prevalence and treatment of vascular anomalies. In addition, in collaboration with Drs Vikkula and Olsen, genetic background has been elucidated for certain forms. For example, due to this tight collaboration, the two teams newly recognised an inherited disorder characterized by atypical capillary malformations associated with fast- flow vascular anomalies (CM-AVM). Using the samples collected by Core C, Project 3 also recently discovered that 49% of sporadic venous malformations are due to somatic hyperphosphorylating TIE2 mutations. Moreover, in collaboration with Project 2 and 3, Project 1 led to the discovery of genetic alterations that play an important role in hemangioma pathophysiology, using samples of this Core. Core C has collected 897 famiUes, 1795 blood samples, 515 tissue samples, and established 135 cell lines. This unique collection of well-characterized samples will be enlarged continuously throughout the Program Project. This allows access of all three Projects of this Program Project to sufficient numbers of samples that are essential for achieving their Aims.

Public Health Relevance

This project aims to collect blood and tissue samples and derive cell-lines from them, from well-characterized patients with vascular anomalies, also known as "angiomas". Such a resource enables efficient research studies to identify the causes of these disorders. Therefore, more specific, better, treatments can be developed in the future.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Program Projects (P01)
Project #
5P01AR048564-10
Application #
8528333
Study Section
Special Emphasis Panel (ZAR1-EHB-F)
Project Start
Project End
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
10
Fiscal Year
2013
Total Cost
$155,592
Indirect Cost
$53,508
Name
Harvard University
Department
Type
DUNS #
047006379
City
Boston
State
MA
Country
United States
Zip Code
02115
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Lee, D; Boscolo, E; Durham, J T et al. (2014) Propranolol targets the contractility of infantile haemangioma-derived pericytes. Br J Dermatol 171:1129-37
Dellinger, Michael T; Garg, Nupur; Olsen, Bjorn R (2014) Viewpoints on vessels and vanishing bones in Gorham-Stout disease. Bone 63:47-52
Uebelhoer, Melanie; Natynki, Marjut; Kangas, Jaakko et al. (2013) Venous malformation-causative TIE2 mutations mediate an AKT-dependent decrease in PDGFB. Hum Mol Genet 22:3438-48
Amyere, Mustapha; Aerts, Virginie; Brouillard, Pascal et al. (2013) Somatic uniparental isodisomy explains multifocality of glomuvenous malformations. Am J Hum Genet 92:188-96
Butler, Matthew G; Dagenais, Susan L; Garcia-Perez, Jose L et al. (2012) Microcephaly, intellectual impairment, bilateral vesicoureteral reflux, distichiasis, and glomuvenous malformations associated with a 16q24.3 contiguous gene deletion and a Glomulin mutation. Am J Med Genet A 158A:839-49
Greenberger, Shoshana; Yuan, Siming; Walsh, Logan A et al. (2011) Rapamycin suppresses self-renewal and vasculogenic potential of stem cells isolated from infantile hemangioma. J Invest Dermatol 131:2467-76
Goujon, Elisa; Cordoro, Kelly M; Barat, Muriel et al. (2011) Congenital plaque-type glomuvenous malformations associated with fetal pleural effusion and ascites. Pediatr Dermatol 28:528-31
Boon, Laurence M; Ballieux, Fanny; Vikkula, Miikka (2011) Pathogenesis of vascular anomalies. Clin Plast Surg 38:7-19
Bowen, Margot E; Boyden, Eric D; Holm, Ingrid A et al. (2011) Loss-of-function mutations in PTPN11 cause metachondromatosis, but not Ollier disease or Maffucci syndrome. PLoS Genet 7:e1002050

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