Somatic mosaicism in von Hippel-Lindau disease

Murgia, Alessandra; Martella, Maddalena; Vinanzi, Cinzia; Polli, Roberta; Perilongo, Giorgio; Opocher, Giuseppe

doi:10.1002/(sici)1098-1004(200001)15:1<114::aid-humu20>3.0.co;2-7

Cited by 69 publications

(22 citation statements)

References 15 publications

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“…De novo germline and mosaic mutations have been documented in VHL patients [Martin et al, 1996;Murgia et al, 2000;Sgambati et al, 2000]. Our consolidated data (Supp .…”

Section: De Novo Germline Mutations and Mosaicismmentioning

confidence: 70%

Genetic analysis of von Hippel-Lindau disease

et al. 2010

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Mutations in the von Hippel-Lindau (VHL) gene are responsible for VHL disease, congenital polycythemia, and are found in many sporadic tumor types as well. Reports of VHL mutations are dispersed throughout original articles and databases that have not been recently updated. We compiled a comprehensive mutation table of 1,548 germline and somatic VHL mutations, derived from this protein of only 213 amino acids. We describe detailed phenotype and gene mutation information for 945 VHL families, including 30 previously unpublished kindreds from The Netherlands (six novel mutations). These data represent the most extensive catalog of germline VHL mutations to date. We also review VHL disease, known and theorized pathogenesis of common VHL manifestations, and genotype-phenotype correlations. Analysis of all VHL families, excluding germline mutations resulting in congenital polycythemias, describes the spectrum of mutation types: 52% missense, 13% frameshift, 11% nonsense, 6% in-frame deletions/insertions, 11% large/complete deletions, and 7% splice mutations. This easy-to-use compilation of VHL mutations is intended to facilitate research and function as a necessary adjunct for physicians when providing patient information. Hum Mutat 31:521-537,

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“…De novo germline and mosaic mutations have been documented in VHL patients [Martin et al, 1996;Murgia et al, 2000;Sgambati et al, 2000]. Our consolidated data (Supp .…”

Section: De Novo Germline Mutations and Mosaicismmentioning

confidence: 70%

Genetic analysis of von Hippel-Lindau disease

et al. 2010

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“…EPAS1 mosaic mutations have been detected in patients with multiple paragangliomas, duodenal somatostatinomas and polycythaemia 80,83 . Pituitary adenomas were reported in patients with PPGLs in familial settings in which an SDH mutation was detected 84,85 .…”

Section: Discussionmentioning

confidence: 99%

“…Both NF1 and VHL, which are established PPGL susceptibility genes, have been detected as mosaic, post-zygotic mutations in neurofibromatosis type 1 or von Hippel-Lindau syndrome; however, this finding has not been described in the specific setting of PPGLs 79,80 . In 2015, mosaic mutations leading to a syndrome involving PPGL and giant cell tumours of bone were reported in association with the H3F3A gene 14 .…”

Section: Box 1 | Features Unique To Ppglsmentioning

confidence: 99%

Consensus Statement on next-generation-sequencing-based diagnostic testing of hereditary phaeochromocytomas and paragangliomas

et al. 2016

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Phaeochromocytomas and paragangliomas (PPGLs) are neural-crest-derived tumours of the sympathetic or parasympathetic nervous system that are often inherited and are genetically heterogeneous. Genetic testing is recommended for patients with these tumours and for family members of patients with hereditary forms of PPGLs. Due to the large number of susceptibility genes implicated in the diagnosis of inherited PPGLs, next-generation sequencing (NGS) technology is ideally suited for carrying out genetic screening of these individuals. This Consensus Statement, formulated by a study group comprised of experts in the field, proposes specific recommendations for the use of diagnostic NGS in hereditary PPGLs. In brief, the study group recommends target gene panels for screening of germ line DNA, technical adaptations to address different modes of disease transmission, orthogonal validation of NGS findings, standardized classification of variant pathogenicity and uniform reporting of the findings. The use of supplementary assays, to aid in the interpretation of the results, and sequencing of tumour DNA, for identification of somatic mutations, is encouraged. In addition, the study group launches an initiative to develop a gene-centric curated database of PPGL variants, with annual re-evaluation of variants of unknown significance by an expert group for purposes of reclassification and clinical guidance.

Funding Agencies|Cancer Prevention and Research Institute of Texas (CPRIT) [RP101202, RP57154]; Department of Defense [CDMRP W81XWH-12-1-0508]; Voelcker Fund; National Institutes of Health (NIH)s National Center for Research Resources; National Center for Advancing Translational Sciences [8UL1TR000149]; INSERM; French National Cancer Institute (INCA); Direction Generale de lOffre de Soins (DGOS); INCA [INCA-DGOS_8663]; European Union [633983]; Brazilian National Council for Scientific and Technological Development (CNPq); Cancer Research for PErsonalized Medicine (CARPEM); ERC Advanced Researcher Award

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“…In other words, patients with VHL disease are VHLϩ/Ϫ heterozygotes. Some VHL patients without a positive family history have, upon further investigation, been found to have a parent who is mosaic for a VHL mutation (presumably as the result of a de novo mutation during early development) (7,8). Tumor development in VHL disease is linked to inactivation or loss of the remaining wild-type VHL allele in a susceptible cell, which leads to loss of the VHL gene product pVHL.…”

Section: Von Hippel-lindau Diseasementioning

confidence: 99%

The von Hippel-Lindau Gene, Kidney Cancer, and Oxygen Sensing

Kaelin¹

2003

Journal of the American Society of Nephrology

119

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Abstract. Recent studies of a relatively rare hereditary cancer syndrome, von Hippel-Lindau (VHL) disease, have shed new light on the molecular pathogenesis of kidney cancer and, perhaps more important, on how mammalian cells sense and respond to changes in oxygen availability. This knowledge is already translating into new therapeutic targets for kidney cancer as well as for multiple conditions, such as myocardial infarction and stroke, in which ischemia plays a pathogenic role. This review summarizes the current knowledge of the molecular pathogenesis of von Hippel-Lindau disease and the role of the VHL gene product (pVHL) in kidney cancer and the mammalian oxygen sensing pathway.

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Somatic mosaicism in von Hippel-Lindau disease

Cited by 69 publications

References 15 publications

Genetic analysis of von Hippel-Lindau disease

Genetic analysis of von Hippel-Lindau disease

Consensus Statement on next-generation-sequencing-based diagnostic testing of hereditary phaeochromocytomas and paragangliomas

The von Hippel-Lindau Gene, Kidney Cancer, and Oxygen Sensing

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