VHL mosaicism: the added value of multi-tissue analysis

被引：0
作者：
Leslie E. Oldfield
Jessica Grzybowski
Sylvie Grenier
Elizabeth Chao
Gregory S. Downs
Kirsten M. Farncombe
Tracy L. Stockley
Ozgur Mete
Raymond H. Kim
机构：
[1] Princess Margaret Cancer Centre,Division of Clinical Laboratory Genetics, Laboratory Medicine Program
[2] Ambry Genetics,Toronto General Hospital Research Institute
[3] University Health Network,Department of Laboratory Medicine and Pathobiology
[4] University Health Network,Princess Margaret Cancer Centre
[5] University of Toronto,undefined
[6] University Health Network,undefined
[7] Sinai Health System,undefined
[8] Hospital for Sick Children,undefined
[9] Department of Medicine,undefined
[10] University of Toronto,undefined
来源：
npj Genomic Medicine | / 7卷
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摘要：
Von Hippel-Lindau disease (VHL) is an autosomal dominant, inherited syndrome with variants in the VHL gene causing predisposition to multi-organ benign and malignant neoplasms. A germline VHL variant is identified in 95–100% of individuals with a clinical diagnosis of VHL. Here, we present the case of an individual with a clinical diagnosis of VHL disease where peripheral blood DNA analysis did not detect a VHL variant. Sequencing of four tumor tissues (ccRCC, pheochromocytoma, lung via sputum, liver) revealed a VHL c.593 T > C (p.Leu198Pro) variant at varying allele fractions (range: 10–55%) in all tissues. Re-examination of the peripheral blood sequencing data identified this variant at 6% allele fraction. Tumor analysis revealed characteristic cytomorphological, immunohistochemical reactivity for alpha-inhibin, and CAIX, and reduced pVHL reactivity supported VHL-related pseudohypoxia. This report of a rare case of VHL mosaicism highlights the value of tissue testing in VHL variant negative cases.
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