학술논문
Development of a Data Portal for Aggregation and Analysis of Genomics Data in Familial Platelet Disorder with Predisposition to Myeloid Malignancy - the RUNX1.DB
Document Type
Article
Author
Brown, Anna L.; Armstrong, Mark; Lawrence, David; Wang, Paul; Arts, Peer; Duployez, Nicolas; Churpek, Jane; Tawana, Kiran; Degelman, Erin; Natsoulis, Georges; Guzman, Monica L.; Patnaik, Mrinal M.; Shimamura, Akiko; Cantor, Alan B.; Ripperger, Tim; Schlegelberger, Brigitte; Steinemann, Doris; DiNardo, Courtney D.; Mecucci, Cristina; Velloso, Elvira DRP; Santos, Fabio PS; Silva, Marcela CA; Borate, Uma; McWeeney, Shannon K.; Nalepa, Grzegorz; Ragg, Susanne; Kwon, Erika Mijin; Agarwal, Anupriya; Langabeer, Stephen; Klco, Jeffery M.; Yang, Jun J.; Forsyth, Cecily; Mapp, Sally; Mar Fan, Helen; Rawlings, Lesley; Susman, Rachel; Morgan, Sue; Wei, Andrew H; Dokal, Inderjeet; Vulliamy, Tom; Hiwase, Devendra K; Singhal, Deepak; Branford, Susan; Papaemmanuil, Elli; Soulier, Jean; Fröhling, Stefan; Kramer, Alwin; Sauvageau, Guy; Morgan, Neil; Owen, Carolyn; Bödör, Csaba; Fitzgibbon, Jude; Rienhoff, Hugh Y.; Kurokawa, Mineo; Godley, Lucy; Preudhomme, Claude; Liu, Paul P; Poplawski, Nicola; Hahn, Christopher N.; Scott, Hamish S.
Source
Blood; November 2018, Vol. 132 Issue: 1, Number 1 Supplement 1 p5241-5241, 1p
Subject
Language
ISSN
00064971; 15280020
Abstract
Background:It has been known for approximately 19 years that germline mutations in RUNX1, lead to familial platelet disorder with predisposition to myeloid malignancy (FPD-MM, OMIM 601399). Since that time researchers have identified a broad range of different RUNX1mutations, in over 100 families. In large families, the diagnosis of malignancy shows variable penetrance among family members with the same mutation; some carriers of RUNX1mutations do not develop malignancy. The causes of this heterogeneity are currently not known, complicating counselling and risk analysis for individual carriers. Recent advances in genetic sequencing technology applied by many FPD-MM research groups around the world have highlighted their value in understanding the somatic genetic changes that are associated with development of malignancies in germline RUNX1mutation carriers. Collectively this information could lead to powerful insights essential for more precise risk assessment, monitoring, and therapeutic intervention. Specifically, a growing catalogue of somatic mutations associated with germline RUNX1malignancy offers the opportunity for informed monitoring of asymptomatic RUNX1carriers for additional high-risk somatic mutations, in turn providing the possibility for early therapeutic intervention to arrest the leukemic process. The challenge in advancing these goals for FPD-MM is the relative rarity of the disorder in individual populations. Global data sharing in a highly interactive FPD-MM research community offers a solution to this problem that benefits all patients world-wide.