Abstract 2102: A comparative study of tissue and blood samples reveals the frequency and characteristics of BRCA and PALB2 mutations in Chinese pancreatic cancer
Authors: Yue Zhu, Yanli Wang, Wenfen Lu, Zhihui Lu, Guihe Huang
Journal: Cancer Research (2025)

Abstract Background and Purpose: Pancreatic cancer is a highly lethal malignancy often associated with genetic mutations, particularly in the BRCA1, BRCA2, and PALB2 genes. Identifying mutations in these genes is crucial for understanding the genetic basis of the disease, guiding treatment decisions, and providing genetic counseling. This study aims to evaluate the mutation frequency and types of BRCA1, BRCA2, and PALB2 in pancreatic cancer patients using both tissue and blood samples through next-generation sequencing (NGS) with a 733-gene panel. Methods: A total of 1425 pancreatic cancer patients were included in this study, with 1228 patients undergoing tissue-based NGS and 197 patients undergoing blood-based NGS. The mutation frequencies, along with the proportions of germline and somatic mutations for BRCA1, BRCA2, and PALB2, were calculated and analyzed. Results: The overall mutation frequency for BRCA1 was (772/1425) 54.18%, with (762/772) 98.7% being germline mutations and (10/772) 1.3% being somatic mutations. In tissue samples, the BRCA1 mutation detection rate was (769/1228) 62.62% (germline: 98.83%; somatic: 1.17%). However, the blood sample analysis yielded a significantly lower detection rate of (3/197) 1.52%, comprising 66.67% germline and 33.33% somatic mutations. For BRCA2, the mutation frequency was (136/1425) 9.54%, with 79.41% being germline alterations; the rates were (132/1228) 10.75% in tissue (germline accounted for 78.79%) and (4/197)2.03% in blood samples, the latter consisting entirely of germline mutations. PALB2 mutations had a frequency of (61/1425) 4.28%, with germline alterations accounting for 93.44%. Tissue analysis showed a PLAB2 mutation detection rate of (59/1228) 4.8% (germline accounted for 93.22%), whereas blood samples showed a rate of (2/197) 1.02%, all being germline mutations. Notably, nonsynonymous mutations were the most prevalent mutation type across all genes in both tissue and blood analyses. Conclusion: The study reveals significant differences in the mutation frequencies and types of BRCA1, BRCA2, and PALB2 detected in pancreatic cancer patients, highlighting higher rates in tissue samples compared to blood samples. The predominance of germline mutations, particularly in BRCA1 and PALB2, emphasizes the importance of genetic testing for personalized treatment strategies and risk assessment in this patient population. These findings contribute valuable insights into the genetic landscape of pancreatic cancer and underscore the need for further investigation into the clinical implications of these mutations. Citation Format: Yue Zhu, Yanli Wang, Wenfen Lu, Zhihui Lu, Guihe Huang. A comparative study of tissue and blood samples reveals the frequency and characteristics of BRCA and PALB2 mutations in Chinese pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2102.