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Fanconi Anaemia, Childhood Cancer and the BRCA Genes
Fanconi anaemia (FA) is an inherited chromosomal instability disorder characterised by congenital and developmental abnormalities and a strong cancer predisposition. In less than 5% of cases FA can be caused by bi-allelic pathogenic variants (PGVs) in BRCA2/FANCD1 and in very rare cases by bi-alleli...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8535386/ https://www.ncbi.nlm.nih.gov/pubmed/34680915 http://dx.doi.org/10.3390/genes12101520 |
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author | Woodward, Emma R. Meyer, Stefan |
author_facet | Woodward, Emma R. Meyer, Stefan |
author_sort | Woodward, Emma R. |
collection | PubMed |
description | Fanconi anaemia (FA) is an inherited chromosomal instability disorder characterised by congenital and developmental abnormalities and a strong cancer predisposition. In less than 5% of cases FA can be caused by bi-allelic pathogenic variants (PGVs) in BRCA2/FANCD1 and in very rare cases by bi-allelic PGVs in BRCA1/FANCS. The rarity of FA-like presentation due to PGVs in BRCA2 and even more due to PGVs in BRCA1 supports a fundamental role of the encoded proteins for normal development and prevention of malignant transformation. While FA caused by BRCA1/2 PGVs is strongly associated with distinct spectra of embryonal childhood cancers and AML with BRCA2-PGVs, and also early epithelial cancers with BRCA1 PGVs, germline variants in the BRCA1/2 genes have also been identified in non-FA childhood malignancies, and thereby implying the possibility of a role of BRCA PGVs also for non-syndromic cancer predisposition in children. We provide a concise review of aspects of the clinical and genetic features of BRCA1/2-associated FA with a focus on associated malignancies, and review novel aspects of the role of germline BRCA2 and BRCA1 PGVs occurring in non-FA childhood cancer and discuss aspects of clinical and biological implications. |
format | Online Article Text |
id | pubmed-8535386 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-85353862021-10-23 Fanconi Anaemia, Childhood Cancer and the BRCA Genes Woodward, Emma R. Meyer, Stefan Genes (Basel) Review Fanconi anaemia (FA) is an inherited chromosomal instability disorder characterised by congenital and developmental abnormalities and a strong cancer predisposition. In less than 5% of cases FA can be caused by bi-allelic pathogenic variants (PGVs) in BRCA2/FANCD1 and in very rare cases by bi-allelic PGVs in BRCA1/FANCS. The rarity of FA-like presentation due to PGVs in BRCA2 and even more due to PGVs in BRCA1 supports a fundamental role of the encoded proteins for normal development and prevention of malignant transformation. While FA caused by BRCA1/2 PGVs is strongly associated with distinct spectra of embryonal childhood cancers and AML with BRCA2-PGVs, and also early epithelial cancers with BRCA1 PGVs, germline variants in the BRCA1/2 genes have also been identified in non-FA childhood malignancies, and thereby implying the possibility of a role of BRCA PGVs also for non-syndromic cancer predisposition in children. We provide a concise review of aspects of the clinical and genetic features of BRCA1/2-associated FA with a focus on associated malignancies, and review novel aspects of the role of germline BRCA2 and BRCA1 PGVs occurring in non-FA childhood cancer and discuss aspects of clinical and biological implications. MDPI 2021-09-27 /pmc/articles/PMC8535386/ /pubmed/34680915 http://dx.doi.org/10.3390/genes12101520 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Woodward, Emma R. Meyer, Stefan Fanconi Anaemia, Childhood Cancer and the BRCA Genes |
title | Fanconi Anaemia, Childhood Cancer and the BRCA Genes |
title_full | Fanconi Anaemia, Childhood Cancer and the BRCA Genes |
title_fullStr | Fanconi Anaemia, Childhood Cancer and the BRCA Genes |
title_full_unstemmed | Fanconi Anaemia, Childhood Cancer and the BRCA Genes |
title_short | Fanconi Anaemia, Childhood Cancer and the BRCA Genes |
title_sort | fanconi anaemia, childhood cancer and the brca genes |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8535386/ https://www.ncbi.nlm.nih.gov/pubmed/34680915 http://dx.doi.org/10.3390/genes12101520 |
work_keys_str_mv | AT woodwardemmar fanconianaemiachildhoodcancerandthebrcagenes AT meyerstefan fanconianaemiachildhoodcancerandthebrcagenes |