Combined germline pathogenic variants in FLCN and TP53 are associated with early onset renal cell carcinoma and brain tumors

Irma van de Beek; Iris E. Glykofridis; Anja Wagner; Dorine T. den Toom; Ernie M.H.F. Bongers; Geert J.L.H. van Leenders; Paul C. Johannesma; Hanne E.J. Meijers-Heijboer; Rob M.F. Wolthuis; Maurice A.M. van Steensel; Hendrikus J. Dubbink; Arjan C. Houweling

doi:10.1002/mgg3.2098

Combined germline pathogenic variants in FLCN and TP53 are associated with early onset renal cell carcinoma and brain tumors

Irma van de Beek, Iris E. Glykofridis, Anja Wagner, Dorine T. den Toom, Ernie M.H.F. Bongers, Geert J.L.H. van Leenders, Paul C. Johannesma, Hanne E.J. Meijers-Heijboer, Rob M.F. Wolthuis, Maurice A.M. van Steensel, Hendrikus J. Dubbink, Arjan C. Houweling^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

13 Downloads (Pure)

Abstract

Background: We present a family consisting of a father and his two children with an exceptional phenotype of childhood renal cell carcinoma and brain tumors. Extensive genetic testing revealed two inherited tumor predisposition syndromes in all three family members: Birt-Hogg-Dubé syndrome and Li-Fraumeni syndrome. The corresponding genes (FLCN and TP53) are both located on the short arm of chromosome 17.

Methods: We describe the phenotype and performed single nucleotide polymorphism (SNP)-based loss of heterozygosity (LOH) analysis of the tumors.

Results: All examined tumors showed somatic loss of the wild-type alleles of both FLCN and TP53.

Conclusions: We hypothesize that a synergistic effect of both mutations caused the unusual phenotype of childhood renal cell carcinoma in this family. This family emphasizes the importance of further genetic testing if a tumor develops at an unexpected young age in an inherited cancer predisposition syndrome.

Original language	English
Article number	e2098
Number of pages	10
Journal	Molecular Genetics and Genomic Medicine
Volume	11
Issue number	2
Early online date	16 Nov 2022
DOIs	https://doi.org/10.1002/mgg3.2098
Publication status	Published - Feb 2023

Bibliographical note

Funding Information: We thank Tom Carney, Monique Luijten, Arnette Wong, Ivo de Vos, Xinhong Lim and Barry Coull for their contributions to the experiments on zebrafish with mutations in both flcn and tp53. The zebrafish experiments mentioned in the discussion were funded by the A*STAR Research Attachment Programme and the Nijbakker Morra stichting.

Publisher Copyright: © 2022 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1002/mgg3.2098Licence: CC BY-NC-ND

Molec Gen Gen Med - 2022 - Beek - Combined germline pathogenic variants in FLCN and TP53 are associated with early onsetFinal published version, 1.17 MBLicence: CC BY-NC-ND

Cite this

van de Beek, I., Glykofridis, I. E., Wagner, A., den Toom, D. T., Bongers, E. M. H. F., van Leenders, G. J. L. H., Johannesma, P. C., Meijers-Heijboer, H. E. J., Wolthuis, R. M. F., van Steensel, M. A. M., Dubbink, H. J., & Houweling, A. C. (2023). Combined germline pathogenic variants in FLCN and TP53 are associated with early onset renal cell carcinoma and brain tumors. Molecular Genetics and Genomic Medicine, 11(2), [e2098]. https://doi.org/10.1002/mgg3.2098

@article{834eaf12a38d42ff9ad1b5a111cbbcd3,

title = "Combined germline pathogenic variants in FLCN and TP53 are associated with early onset renal cell carcinoma and brain tumors",

abstract = "Background: We present a family consisting of a father and his two children with an exceptional phenotype of childhood renal cell carcinoma and brain tumors. Extensive genetic testing revealed two inherited tumor predisposition syndromes in all three family members: Birt-Hogg-Dub{\'e} syndrome and Li-Fraumeni syndrome. The corresponding genes (FLCN and TP53) are both located on the short arm of chromosome 17. Methods: We describe the phenotype and performed single nucleotide polymorphism (SNP)-based loss of heterozygosity (LOH) analysis of the tumors. Results: All examined tumors showed somatic loss of the wild-type alleles of both FLCN and TP53. Conclusions: We hypothesize that a synergistic effect of both mutations caused the unusual phenotype of childhood renal cell carcinoma in this family. This family emphasizes the importance of further genetic testing if a tumor develops at an unexpected young age in an inherited cancer predisposition syndrome.",

author = "{van de Beek}, Irma and Glykofridis, {Iris E.} and Anja Wagner and {den Toom}, {Dorine T.} and Bongers, {Ernie M.H.F.} and {van Leenders}, {Geert J.L.H.} and Johannesma, {Paul C.} and Meijers-Heijboer, {Hanne E.J.} and Wolthuis, {Rob M.F.} and {van Steensel}, {Maurice A.M.} and Dubbink, {Hendrikus J.} and Houweling, {Arjan C.}",

note = "Funding Information: We thank Tom Carney, Monique Luijten, Arnette Wong, Ivo de Vos, Xinhong Lim and Barry Coull for their contributions to the experiments on zebrafish with mutations in both flcn and tp53. The zebrafish experiments mentioned in the discussion were funded by the A*STAR Research Attachment Programme and the Nijbakker Morra stichting. Publisher Copyright: {\textcopyright} 2022 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.",

year = "2023",

month = feb,

doi = "10.1002/mgg3.2098",

language = "English",

volume = "11",

journal = "Molecular genetics & genomic medicine",

issn = "2324-9269",

publisher = "John Wiley & Sons Inc.",

number = "2",

}

van de Beek, I, Glykofridis, IE, Wagner, A, den Toom, DT, Bongers, EMHF, van Leenders, GJLH, Johannesma, PC, Meijers-Heijboer, HEJ, Wolthuis, RMF, van Steensel, MAM, Dubbink, HJ & Houweling, AC 2023, 'Combined germline pathogenic variants in FLCN and TP53 are associated with early onset renal cell carcinoma and brain tumors', Molecular Genetics and Genomic Medicine, vol. 11, no. 2, e2098. https://doi.org/10.1002/mgg3.2098

TY - JOUR

T1 - Combined germline pathogenic variants in FLCN and TP53 are associated with early onset renal cell carcinoma and brain tumors

AU - van de Beek, Irma

AU - Glykofridis, Iris E.

AU - Wagner, Anja

AU - den Toom, Dorine T.

AU - Bongers, Ernie M.H.F.

AU - van Leenders, Geert J.L.H.

AU - Johannesma, Paul C.

AU - Meijers-Heijboer, Hanne E.J.

AU - Wolthuis, Rob M.F.

AU - van Steensel, Maurice A.M.

AU - Dubbink, Hendrikus J.

AU - Houweling, Arjan C.

N1 - Funding Information: We thank Tom Carney, Monique Luijten, Arnette Wong, Ivo de Vos, Xinhong Lim and Barry Coull for their contributions to the experiments on zebrafish with mutations in both flcn and tp53. The zebrafish experiments mentioned in the discussion were funded by the A*STAR Research Attachment Programme and the Nijbakker Morra stichting. Publisher Copyright: © 2022 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.

PY - 2023/2

Y1 - 2023/2

N2 - Background: We present a family consisting of a father and his two children with an exceptional phenotype of childhood renal cell carcinoma and brain tumors. Extensive genetic testing revealed two inherited tumor predisposition syndromes in all three family members: Birt-Hogg-Dubé syndrome and Li-Fraumeni syndrome. The corresponding genes (FLCN and TP53) are both located on the short arm of chromosome 17. Methods: We describe the phenotype and performed single nucleotide polymorphism (SNP)-based loss of heterozygosity (LOH) analysis of the tumors. Results: All examined tumors showed somatic loss of the wild-type alleles of both FLCN and TP53. Conclusions: We hypothesize that a synergistic effect of both mutations caused the unusual phenotype of childhood renal cell carcinoma in this family. This family emphasizes the importance of further genetic testing if a tumor develops at an unexpected young age in an inherited cancer predisposition syndrome.

AB - Background: We present a family consisting of a father and his two children with an exceptional phenotype of childhood renal cell carcinoma and brain tumors. Extensive genetic testing revealed two inherited tumor predisposition syndromes in all three family members: Birt-Hogg-Dubé syndrome and Li-Fraumeni syndrome. The corresponding genes (FLCN and TP53) are both located on the short arm of chromosome 17. Methods: We describe the phenotype and performed single nucleotide polymorphism (SNP)-based loss of heterozygosity (LOH) analysis of the tumors. Results: All examined tumors showed somatic loss of the wild-type alleles of both FLCN and TP53. Conclusions: We hypothesize that a synergistic effect of both mutations caused the unusual phenotype of childhood renal cell carcinoma in this family. This family emphasizes the importance of further genetic testing if a tumor develops at an unexpected young age in an inherited cancer predisposition syndrome.

UR - http://www.scopus.com/inward/record.url?scp=85143209337&partnerID=8YFLogxK

U2 - 10.1002/mgg3.2098

DO - 10.1002/mgg3.2098

M3 - Article

C2 - 36382415

AN - SCOPUS:85143209337

SN - 2324-9269

VL - 11

JO - Molecular genetics & genomic medicine

JF - Molecular genetics & genomic medicine

IS - 2

M1 - e2098

ER -

Combined germline pathogenic variants in FLCN and TP53 are associated with early onset renal cell carcinoma and brain tumors

Abstract

Bibliographical note

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this