1. RAD51B Harbors Germline Mutations Associated With Pancreatic Ductal Adenocarcinoma.
- Author
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Xie, Fanfan, Ding, Ding, Lin, Cong, Cunningham, Dea, Wright, Michael, Javed, Ammar A., Azad, Nilo, Lee, Valerie, Donehower, Ross, De Jesus-Acosta, Ana, Le, Dung T., Pishvaian, Michael, Shin, Eun Ji, Lennon, Anne Marie, Khashab, Mouen, Singh, Vikesh, Klein, Alison P., Roberts, Nicholas J., Hacker-Prietz, Amy, and McPhaul, Thomas
- Subjects
DNA repair ,PANCREATIC duct ,GENETIC recombination ,DNA mismatch repair ,GERM cells ,HEREDITARY cancer syndromes ,NUCLEOTIDE sequencing ,HARBORS ,GENETIC mutation - Abstract
PURPOSE: Genetic alterations in many components of the homologous recombination, DNA damage response, and repair (HR-DDR) pathway are involved in the hereditary cancer syndromes, including familial pancreatic cancer. HR-DDR genes beyond BRCA1 , BRCA2 , ATM , and PALB2 may also mutate and confer the HR-DDR deficiency in pancreatic ductal adenocarcinoma (PDAC). METHODS: We conducted a study to examine the genetic alterations using a companion diagnostic 15-gene HR-DDR panel in PDACs. HR-DDR gene mutations were identified and characterized by whole-exome sequencing and whole-genome sequencing. Different HR-DDR gene mutations are associated with variable homologous recombination deficiency (HRD) scores. RESULTS: Eight of 50 PDACs with at least one HR-DDR gene mutation were identified. One tumor with BRCA2 mutations is associated with a high HRD score. However, another tumor with a CHEK2 mutation is associated with a zero HRD score. Notably, four of eight PDACs in this study harbor a RAD51B gene mutation. All four RAD51B gene mutations were germline mutations. However, currently, RAD51B is not the gene panel for germline tests. CONCLUSION: The finding in this study thus supports including RAD51B in the germline test of HR-DDR pathway genes. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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