PALB2 analysis in BRCA2-like families
M A Adank1, S E van Mil, J J P Gille
1Department of Clinical Genetics, VU Medical Center, HV, Amsterdam, The Netherlands.
Breast Cancer Research and Treatment
|June 29, 2010
Summary
Germline mutations in PALB2 do not significantly increase cancer risk in families with ovarian, male breast, or pancreatic cancers. This study investigated PALB2 mutations in non-BRCA1/2 cancer families, finding limited contribution.
Area of Science:
- Genetics
- Oncology
- Molecular Biology
Background:
- BRCA2 and PALB2 proteins are crucial for DNA repair within the Fanconi anemia (FA)-Breast Cancer (BRCA) pathway.
- Germline mutations in BRCA2 and PALB2 are associated with increased risks of female breast and pancreatic cancers, and biallelic mutations cause Fanconi anemia.
Purpose of the Study:
- To investigate the prevalence of PALB2 mutations in breast cancer families with BRCA2-associated tumors beyond female breast cancer.
- To assess the contribution of PALB2 mutations to cancer risk in specific non-BRCA1/2 cancer families.
Main Methods:
- PALB2 mutation analysis was conducted on 110 patients diagnosed with non-BRCA1/2 cancers.
- Patient cohorts included those with ovarian cancer, breast cancer with pancreatic cancer family history, and male breast cancer.
Main Results:
- One truncating PALB2 mutation (c.509_510delGA, p.Arg170X) was identified in a male breast cancer patient.
- No significant contribution of germline PALB2 mutations was observed in the studied non-BRCA1/2 cancer families.
Conclusions:
- Germline PALB2 mutations do not appear to be a significant risk factor for ovarian, male breast, or pancreatic cancers in the absence of BRCA1/2 mutations.
- The findings suggest that PALB2 screening may not be warranted for these specific cancer family histories.
Related Concept Videos
01:35Pedigree Analysis
Overview
01:35Pedigree Analysis
Overview
01:49Probability Laws
Overview
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
01:02Long-patch Base Excision Repair
Since the discovery of the two BER pathways, there has been a debate about how a cell chooses one pathway over the other and the factors determining this selection. Numerous in vitro experiments have pointed out multiple determinants for the sub-pathway selection. These are: