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Gene of the month: PALB2
Omar Hamdan1, Klaudia M Nowak2
1University Health Network Laboratory Medicine Program, Toronto, Ontario, Canada.
Journal of Clinical Pathology
|January 5, 2023
Summary
The partner and localiser of BRCA2 (PALB2) gene is crucial for DNA repair. While PALB2 mutations are linked to cancers and Fanconi anemia, most variants require further study for clinical use.
Area of Science:
- Genetics
- Molecular Biology
- Oncology
Background:
- The PALB2 gene is a tumor suppressor vital for DNA double-strand break repair via homologous recombination.
- PALB2 facilitates interactions within the BRCA1, BRCA2, and RAD51 pathways.
- Germline heterozygous mutations in PALB2 are associated with increased risks of breast, pancreatic, and ovarian cancers.
Purpose of the Study:
- To review the current understanding of PALB2 gene variants and their clinical significance.
- To highlight the role of PALB2 in DNA repair and its association with various cancers and Fanconi anemia.
Main Methods:
- Literature review of identified PALB2 variants.
- Analysis of mutation databases and clinical reports.
- Assessment of variant pathogenicity and clinical implications.
Main Results:
- 604 distinct PALB2 variants have been identified to date.
- Only 140 variants are currently classified as pathogenic.
- Approximately 400 variants remain of unknown significance, necessitating further research.
Conclusions:
- PALB2 plays a critical role in DNA repair and cancer predisposition.
- The clinical utility of PALB2 variants as biomarkers is limited by the large number of unknown significance variants.
- Further research is essential to accurately classify PALB2 variants for routine clinical application.
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