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Combined germline pathogenic variants in FLCN and TP53 are associated with early onset renal cell carcinoma and brain tumors
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‐Fr...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9938753/ https://www.ncbi.nlm.nih.gov/pubmed/36382415 http://dx.doi.org/10.1002/mgg3.2098 |
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author | van de Beek, Irma Glykofridis, Iris E. Wagner, Anja den Toom, Dorine T. Bongers, Ernie M. H. F. van Leenders, Geert J. L. H. Johannesma, Paul C. Meijers‐Heijboer, Hanne E. J. Wolthuis, Rob M. F. van Steensel, Maurice A. M. Dubbink, Hendrikus J. Houweling, Arjan C. |
author_facet | van de Beek, Irma Glykofridis, Iris E. Wagner, Anja den Toom, Dorine T. Bongers, Ernie M. H. F. van Leenders, Geert J. L. H. Johannesma, Paul C. Meijers‐Heijboer, Hanne E. J. Wolthuis, Rob M. F. van Steensel, Maurice A. M. Dubbink, Hendrikus J. Houweling, Arjan C. |
author_sort | van de Beek, Irma |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9938753 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-99387532023-02-19 Combined germline pathogenic variants in FLCN and TP53 are associated with early onset renal cell carcinoma and brain tumors van de Beek, Irma Glykofridis, Iris E. Wagner, Anja den Toom, Dorine T. Bongers, Ernie M. H. F. van Leenders, Geert J. L. H. Johannesma, Paul C. Meijers‐Heijboer, Hanne E. J. Wolthuis, Rob M. F. van Steensel, Maurice A. M. Dubbink, Hendrikus J. Houweling, Arjan C. Mol Genet Genomic Med Original Articles 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. John Wiley and Sons Inc. 2022-11-16 /pmc/articles/PMC9938753/ /pubmed/36382415 http://dx.doi.org/10.1002/mgg3.2098 Text en © 2022 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Original Articles van de Beek, Irma Glykofridis, Iris E. Wagner, Anja den Toom, Dorine T. Bongers, Ernie M. H. F. van Leenders, Geert J. L. H. Johannesma, Paul C. Meijers‐Heijboer, Hanne E. J. Wolthuis, Rob M. F. van Steensel, Maurice A. M. Dubbink, Hendrikus J. Houweling, Arjan C. Combined germline pathogenic variants in FLCN and TP53 are associated with early onset renal cell carcinoma and brain tumors |
title | Combined germline pathogenic variants in FLCN and TP53 are associated with early onset renal cell carcinoma and brain tumors |
title_full | Combined germline pathogenic variants in FLCN and TP53 are associated with early onset renal cell carcinoma and brain tumors |
title_fullStr | Combined germline pathogenic variants in FLCN and TP53 are associated with early onset renal cell carcinoma and brain tumors |
title_full_unstemmed | Combined germline pathogenic variants in FLCN and TP53 are associated with early onset renal cell carcinoma and brain tumors |
title_short | Combined germline pathogenic variants in FLCN and TP53 are associated with early onset renal cell carcinoma and brain tumors |
title_sort | combined germline pathogenic variants in flcn and tp53 are associated with early onset renal cell carcinoma and brain tumors |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9938753/ https://www.ncbi.nlm.nih.gov/pubmed/36382415 http://dx.doi.org/10.1002/mgg3.2098 |
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