Genome-Wide Uniparental Disomy and Copy Number Variations in Renal Cell Carcinomas Associated with Birt-Hogg-Dubé Syndrome

The American Journal of Pathology
Yasuhiro IribeMitsuko Furuya

Abstract

Birt-Hogg-Dubé syndrome is an inherited disorder caused by germline mutations of the folliculin gene (FLCN). The affected patients are prone to developing renal cell carcinomas (RCCs). Most mutant FLCN-associated RCCs (mFLCN-RCCs) are histologically chromophobe RCCs and hybrid oncocytic/chromophobe tumors. It is incompletely understood whether mFLCN-RCCs have different chromosomal abnormalities compared with their sporadic histological counterparts. Herein, we describe somatic mutations of FLCN and DNA-copy number abnormalities using a high-density, whole-genome, single-nucleotide polymorphism array. The histological types included chromophobe RCC (n = 12), hybrid oncocytic/chromophobe tumor (n = 5), and clear-cell RCC (n = 2). Of 19 tumors, 8 had pathological somatic mutations of FLCN. Among 11 mFLCN-RCCs investigated by single-nucleotide polymorphism array, 8 showed balanced genomic profiles, 2 had gains in chromosome 3q, and 1 had gains in chromosomes 1q and 7. All had copious numbers of loss of heterozygosity in a wide range of chromosomes. The common loss-of-heterozygosity regions were chromosomes 3p24, 8q11, 16q11, Xp22-21, Xp11, Xq11, Xq13, and Xq23. Most of the loss of heterozygosity was because of uniparental disomy. C...Continue Reading

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Citations

Dec 20, 2016·Laboratory Investigation; a Journal of Technical Methods and Pathology·Mitsuko FuruyaMasahiro Yao
Mar 15, 2018·Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG·Ortrud K SteinleinElke C Sattler
Mar 15, 2018·Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG·Ortrud K SteinleinElke C Sattler
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Mar 6, 2021·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Kiril TrpkovAnthony J Gill

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