VHL mosaicism: the added value of multi-tissue analysis

被引：13

作者：

Oldfield, Leslie E. ^{[1
]}

Grzybowski, Jessica ^{[2
]}

Grenier, Sylvie ^{[3
]}

Chao, Elizabeth ^{[2
]}

Downs, Gregory S. ^{[3
]}

Farncombe, Kirsten M. ^{[4
]}

Stockley, Tracy L. ^{[3
,5
]}

Mete, Ozgur ^{[1
]}

Kim, Raymond H. ^{[6
]}

机构：

[1] Princess Margaret Canc Ctr, Toronto, ON, Canada

[2] Ambry Genet, Aliso Viejo, CA USA

[3] Univ Hlth Network, Lab Med Program, Div Clin Lab Genet, Toronto, ON, Canada

[4] Univ Hlth Network, Toronto Gen Hosp, Res Inst, Toronto, ON, Canada

[5] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada

[6] Univ Toronto, Hosp Sick Children, Univ Hlth Network,Dept Med, Princess Margaret Canc Ctr,Sinai Hlth Syst, Toronto, ON, Canada

来源：

NPJ GENOMIC MEDICINE | 2022年 / 7卷 / 01期

关键词：

HIPPEL-LINDAU-DISEASE; GERMLINE MUTATIONS; CANCER; GENE;

D O I：

10.1038/s41525-022-00291-3

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

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.

引用

页数：5

共 40 条

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