GTS5:PALB2-related cancer predisposition syndrome (PALB2): Difference between revisions
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The PALB2 gene is located at chromosome 16p12.2 and contains 13 exons, encoding a 1,186 amino acid protein. PALB2 (Partner and Localizer of BRCA2) is a key component of the homologous recombination (HR) DNA repair pathway, where it directly interacts with BRCA2 to facilitate the accurate repair of DNA double-strand breaks. Through its role in DNA damage repair, PALB2 functions as a tumor suppressor that maintains genomic integrity<ref name=":0" /><ref name=":1" /> | The PALB2 gene is located at chromosome 16p12.2 and contains 13 exons, encoding a 1,186 amino acid protein. PALB2 (Partner and Localizer of BRCA2) is a key component of the homologous recombination (HR) DNA repair pathway, where it directly interacts with BRCA2 to facilitate the accurate repair of DNA double-strand breaks. Through its role in DNA damage repair, PALB2 functions as a tumor suppressor that maintains genomic integrity<ref name=":0" /><ref name=":1" /> | ||
=== Clinical Phenotypes by Zygosity === | |||
===== Heterozygous State (Monoallelic Pathogenic Variants) ===== | |||
Germline heterozygous pathogenic variants in PALB2 confer susceptibility to hereditary cancer syndromes with incomplete penetrance. The most frequently associated malignancies include breast, pancreatic, and ovarian cancers<ref name=":3" /><ref name=":5" />. Germline PALB2 pathogenic variants have also been reported in individuals with prostate, gastric, and colorectal cancers, though penetrance for these cancers is less well established<ref name=":22">Slavin TP, et al. The contribution of pathogenic variants in breast cancer susceptibility genes to familial breast cancer risk. NPJ Breast Cancer. 2017;3:22.</ref>. | |||
====== Cancer risk estimates for heterozygous carriers: ====== | |||
Lifetime breast cancer risk (females): ~35–60% | |||
Relative risk: ~5-fold compared with the general population | |||
Tumor phenotype: Enrichment of triple-negative breast cancer among PALB2-associated breast cancers<ref name=":3" /><ref name=":15" /> | |||
=== PALB2 Related Cancer Predisposition Syndrome: === | === PALB2 Related Cancer Predisposition Syndrome: === | ||
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<ref name=":1" />Sy SMH, Huen MSY, Chen J. PALB2 is an integral component of the BRCA complex required for homologous recombination repair. Proceedings of the National Academy of Sciences USA. 2009;106(17):7155–7160. | <ref name=":1" />Sy SMH, Huen MSY, Chen J. PALB2 is an integral component of the BRCA complex required for homologous recombination repair. Proceedings of the National Academy of Sciences USA. 2009;106(17):7155–7160. | ||
<ref name=":22" />Slavin TP, et al. The contribution of pathogenic variants in breast cancer susceptibility genes to familial breast cancer risk. NPJ Breast Cancer. 2017;3:22. | |||
<ref name=":2" />Park JY, Zhang F, Andreassen PR. PALB2: the hub of a network of tumor suppressors involved in DNA damage responses. Biochimica et Biophysica Acta. 2014;1846(1):263–275. | <ref name=":2" />Park JY, Zhang F, Andreassen PR. PALB2: the hub of a network of tumor suppressors involved in DNA damage responses. Biochimica et Biophysica Acta. 2014;1846(1):263–275. | ||