کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
8716136 1587877 2018 30 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Analyzing the Genetic Spectrum of Vascular Anomalies with Overgrowth via Cancer Genomics
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی امراض پوستی
پیش نمایش صفحه اول مقاله
Analyzing the Genetic Spectrum of Vascular Anomalies with Overgrowth via Cancer Genomics
چکیده انگلیسی
Vascular anomalies are variably associated with overgrowth, skeletal anomalies, and abnormalities of the brain, leptomeninges, and eye. We assembled a 16-institution network to determine the range of genetic variants associated with a spectrum of vascular anomalies with overgrowth, ranging from mild to severe. Because of the overlap between cancer-associated variants and previously described somatic variants in vascular overgrowth syndromes, we employed tumor genetic profiling via high-depth next-generation sequencing using a panel to assay affected tissue from a diverse cohort of subjects with vascular anomalies with overgrowth. Seventy-five percent (43/57) harbored pathogenic or likely pathogenic variants in 10 genes. We identified two genes (mTOR, PIK3R1) and several variants previously described in the setting of cancer but that, to our knowledge, have not been described in vascular malformations. All were identified at low variant allele frequency consistent with somatic mosaic etiology. By leveraging somatic variant detection technology typically applied to cancer in a cohort inclusive of broad phenotypic severity, we demonstrated that most vascular anomalies with overgrowth harbor postzygotic gain-of-function mutations in oncogenes. Furthermore, continued interrogation of oncogenes in benign developmental disorders could provide insight into fundamental mechanisms regulating cell growth.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Investigative Dermatology - Volume 138, Issue 4, April 2018, Pages 957-967
نویسندگان
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