VHL mosaicism: the added value of multi-tissue analysis.

Abstract

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.

• Authors: Leslie E Oldfield, Jessica Grzybowski, Sylvie Grenier, Elizabeth Chao, Gregory S Downs, Kirsten M Farncombe, Tracy L Stockley, Ozgur Mete, Raymond H Kim
• Journal: NPJ genomic medicine (NPJ Genom Med) Vol. 7 Issue 1 Pg. 21 (Mar 18 2022) ISSN: 2056-7944 [Electronic] England
• PMID: 35304467 (Publication Type: Journal Article)
• Copyright: © 2022. The Author(s).