Characterization of a splice-site mutation in the tumor suppressor gene FLCN associated with renal cancer

BMC Medical Genetics
Malte P BartramRoman-Ulrich Müller

Abstract

Renal cell carcinoma is among the most prevalent malignancies. It is generally sporadic. However, genetic studies of rare familial forms have led to the identification of mutations in causative genes such as VHL and FLCN. Mutations in the FLCN gene are the cause of Birt-Hogg-Dubé syndrome, a rare tumor syndrome which is characterized by the combination of renal cell carcinoma, pneumothorax and skin tumors. Using Sanger sequencing we identify a heterozygous splice-site mutation in FLCN in lymphocyte DNA of a patient suffering from renal cell carcinoma. Furthermore, both tumor DNA and DNA from a metastasis are analyzed regarding this mutation. The pathogenic effect of the sequence alteration is confirmed by minigene assays and the biochemical consequences on the protein are examined using TALEN-mediated transgenesis in cultured cells. Here we describe an FLCN mutation in a 55-year-old patient who presented himself with progressive weight loss, bilateral kidney cysts and renal tumors. He and members of his family had a history of recurrent pneumothorax during the last few decades. Histology after tumor nephrectomy showed a mixed kidney cancer consisting of elements of a chromophobe renal cell carcinoma and dedifferentiated small c...Continue Reading

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Citations

Feb 6, 2020·International Braz J Urol : Official Journal of the Brazilian Society of Urology·Laura Cifuentes-CHerney Andres Garcia-Perdomo
Dec 26, 2018·Clinical Kidney Journal·Roman-Ulrich Müller, Thomas Benzing
Nov 3, 2020·PLoS Genetics·Lene ClausenRasmus Hartmann-Petersen

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BETA
PCR
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transfection
biopsies
transgenic
fluorescence imaging
ubiquitination

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alamut visual
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EX SKIP
Exon Primer

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