GTS5:PALB2-related cancer predisposition syndrome (PALB2): Difference between revisions

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-|<span class="blue-text">EXAMPLE:</span> ''BRCA1''||<span class="blue-text">EXAMPLE:</span> Biallelic inactivation variants||<span class="blue-text">EXAMPLE:</span> Second hit mutation can occur as copy neutral LOH, inactivating mutation, deletion, promoter hypermethylation, or a structural abnormality disrupting the gene.||
+|PALB2||Biallelic inactivation (second hit): loss of heterozygosity (LOH), somatic truncating mutation, focal or whole-gene deletion, copy-neutral LOH||Somatic inactivation of the remaining wild-type PALB2 allele in tumors from germline carriers leads to complete loss of PALB2 function, resulting in homologous recombination deficiency, impaired RAD51 loading, and genomic instability||Not inherited; somatic event occurring in tumors of germline carriers; contributes to tumor initiation and progression
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+|Tumor development in PALB2 associated cancers typically follows a two hit model, analogous to BRCA1/2, with somatic loss of the wild-type allele frequently observed in breast and pancreatic tumors <ref name=":0" /><ref name=":1" /><ref name=":2" />. Biallelic loss is associated with HR-deficient genomic signatures and therapeutic sensitivity to DNA-damaging agents and PARP inhibitors<ref name=":2" /><ref name=":3" /><ref name=":4" />
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 |<span class="blue-text">EXAMPLE:</span> ''BRCA1''