Abstract 1962P
Background
DNA damage repair (DDR) deficiency indicates genetic susceptibility and personalized treatment including platinum-based chemotherapy and PARP inhibitors in pancreatic cancer. We aim to assess the characteristics of DDR deficiency in Chinese pancreatic cancer patients.
Methods
Hybrid capture-based next-generation sequencing including 381 or 733 cancer-related genes were performed with matched tumor tissue and whole blood sample from pancreatic cancer patients between January 2017 and March 2020. Genomic alterations including single nucleotide variation, small insertions/deletion, copy number variation, gene fusion and large rearrangement were assessed. Pathogenic and very likely pathogenic mutation in DDR genes were included for analysis. Tumor mutation burden (TMB) was calculated by the counts of somatic mutations including missense, stop loss, in-frame and frameshift mutations in protein coding regions per mega base.
Results
The 884 pancreatic cancers were included for analysis. Five hundred and sixteen (58.4%) were male, and the median age was 58 (range,20-89). Seventy-two (8.1%) patients harbored 94 somatic mutations in 24 DDR genes. The mutation frequency in Homologous Recombination Repair (HRR), Mismatch Repair (MMR), Fanconi Anemia (FA) and DNA Damage Sensor pathway were 29 (3.3%), 16 (1.8%),6 (0.7%) and 29 (3.2%), respectively. The most frequent somatic alternations were ATM (n=26, 2.9%), BRCA2 (n=13, 1.5%) and PMS2 (n=6, 0.7%). In addition, 72 (8.1%) patients were detected with 72 germline mutations in 14 DDR genes. Among these patients, 12 (1.4%) carried somatic and germline DDR alterations simultaneously. Germline mutations in high penetrance genes (21 ATM, 17 BRCA2, 6 PALB2, 3 BRCA1, 1 CHECK1 and 1 PMS2) were found. TMB was borderline higher in patients with somatic or germline DDR alterations comparing with patients without any DDR mutation (median TMB 4.84/Mb vs 4.03/Mb, P=0.05).
Conclusions
In total, 14.9% of pancreatic cancer patients harbored somatic or germline mutations in DDR pathway, who might benefit from platinum-based chemotherapy or PARP inhibitors. Expanded DDR gene sequencing would impact therapeutic strategy and susceptibility management in pancreatic cancer patients.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.