A Recurrent PDGFRB Mutation Causes Familial Infantile Myofibromatosis

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• 作者：Yee Him Cheung¹ ; ²⁰ ; Tenzin Gayden² ; ²⁰ ; Philippe M. Campeau³ ; Charles A. LeDuc¹ ; Donna Russo¹ ; Van-Hung Nguyen⁴ ; Jiancheng Guo¹ ; Ming Qi⁵ ; ⁶ ; ⁷ ; Yanfang Guan⁷ ; Steffen Albrecht⁴ ; Brenda Moroz⁸ ; Karen W. Eldin⁹ ; James T. Lu¹⁰ ; ¹¹ ; Jeremy Schwartzentruber¹² ; David Malkin¹³ ; Albert M. Berghuis¹⁴ ; Sherif Emil¹⁵ ; Richard A. Gibbs¹⁰ ; David L. Burk¹⁴ ; Megan Vanstone¹⁶ ; Brendan H. Lee³ ; ¹⁷ ; David Orchard¹⁸ ; Kym M. Boycott¹⁶ ; Wendy K. Chung¹ ; ^{wkc15@mail.cumc.columbia.edu} ; Nada Jabado² ; ¹⁹ ; ^{nada.jabado@mcgill.ca}
• 刊名：The American Journal of Human Genetics
• 出版年：2013
• 出版时间：6 June, 2013
• 年：2013
• 卷：92
• 期：6
• 页码：996-1000
• 全文大小：522 K

文摘

Infantile myofibromatosis (IM) is the most common benign fibrous tumor of soft tissues affecting young children. By using whole-exome sequencing, RNA sequencing, and targeted sequencing, we investigated germline and tumor DNA in individuals from four distinct families with the familial form of IM and in five simplex IM cases with no previous family history of this disease. We identified a germline mutation c.1681C>T (p.Arg561Cys) in platelet-derived growth factor receptor ¦Â (PDGFRB) in all 11 affected individuals with familial IM, although none of the five individuals with nonfamilial IM had mutations in this gene. We further identified a second heterozygous mutation in PDGFRB in two myofibromas from one of the affected familial cases, indicative of a potential second hit in this gene in the tumor. PDGFR-¦Â promotes growth of mesenchymal cells, including blood vessels and smooth muscles, which are affected in IM. Our findings indicate p.Arg561Cys substitution in PDGFR-¦Â as a cause of the dominant form of this disease. They provide a rationale for further investigations of this specific mutation and gene to assess the benefits of targeted therapies against PDGFR-¦Â in aggressive life-threatening familial forms of the disease.