A systematic review of predicted pathogenic PALB2 variants: an analysis of mutational overlap between epithelial cancers.
BRCA1 Protein
/ genetics
BRCA2 Protein
/ genetics
Breast Neoplasms
/ genetics
Carcinoma, Ovarian Epithelial
/ genetics
Exons
/ genetics
Fanconi Anemia Complementation Group N Protein
/ genetics
Female
Genetic Predisposition to Disease
Germ-Line Mutation
Humans
Ovarian Neoplasms
/ genetics
Pancreatic Neoplasms
/ genetics
Journal
Journal of human genetics
ISSN: 1435-232X
Titre abrégé: J Hum Genet
Pays: England
ID NLM: 9808008
Informations de publication
Date de publication:
Jan 2020
Jan 2020
Historique:
received:
28
05
2019
accepted:
30
09
2019
revised:
21
08
2019
pubmed:
18
10
2019
medline:
14
7
2020
entrez:
18
10
2019
Statut:
ppublish
Résumé
Partner and localiser of BRCA2 forms part of a macromolecular complex with BRCA1 and BRCA2, which is critical for the repair of double-strand DNA breaks by homologous DNA recombination. Germline loss-of-function variants in the PALB2 gene may confer an increased lifetime risk of breast, pancreatic, ovarian and other cancers. However, the complete spectrum of predicted pathogenic PALB2 variants associated with each tissue type of cancer remains unknown. A systematic review is performed with the aim of cataloguing predicted pathogenic PALB2 variants in breast, ovary and pancreas cancers. All catalogued predicted pathogenic variants are analysed to assess for overlap and mutational "hotspots" within gene exons. Our results showed that 911 (92.5%) cases were described in breast cancer patients, 49 (5.0%) cases were described in ovarian cancer patients, and 24 (2.4%) cases were described in pancreatic cancer patients. The top five most frequently reported predicted pathogenic PALB2 variants were c.509_510delGA, c.3113G > A, c.1592delT, c.172_175delTTGT, and c.1240C > T, accounting for 57.3% of all cases. Breast and pancreatic cancers share five variants while breast and ovarian cancers share 12 variants. Breast, ovarian and pancreatic cancers share eight common variants. Exons with the highest mutation rates were exons 2 (6.7%), 1 (6.3%) and 3 (5.8%). This systematic review provides a quantitative catalogue of predicted pathogenic PALB2 variants described in cancers. This comprehensive analysis of the PALB2 mutational spectrum represents a useful resource for clinicians overseeing PALB2-related cancer surveillance and provides a valuable resource for future PALB2-specific research.
Identifiants
pubmed: 31619740
doi: 10.1038/s10038-019-0680-7
pii: 10.1038/s10038-019-0680-7
doi:
Substances chimiques
BRCA1 Protein
0
BRCA1 protein, human
0
BRCA2 Protein
0
BRCA2 protein, human
0
Fanconi Anemia Complementation Group N Protein
0
PALB2 protein, human
0
Types de publication
Journal Article
Systematic Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
199-205Subventions
Organisme : Pancreatic Cancer UK
ID : 2018RIF_06
Pays : United Kingdom
Organisme : Medical Research Council
ID : G1002543
Pays : United Kingdom
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