Abstract 1541P
Background
Pancreatic adenocarcinoma (PAC) remains one of the most deadly diseases. KRAS, TP53, CDKN2A and SMAD4 are the four major driver genes. PARP inhibitor olaparib for germline BRCA-mutated pancreatic cancer is approved in the front-line maintenance. However, the distribution of genomic alterations associated with prognosis and treatment of Chinese PACs remains unknown.
Methods
540 Chinese PAC patients were enrolled in this study. Next-generation sequencing targeting 450 cancer genes was performed on formalin-fixed, paraffin-embedded (FFPE) tumor tissues and matching blood samples. Genomic alterations included single base substitution, short and long insertion/deletion (Indel), copy number variation, gene fusion and rearrangement. Tumor mutational burden (TMB) and microsatellite instability (MSI) were assessed.
Results
This cohort included 308 male and 232 female. Germline mutations were identified in 60 patients (11.1%), including 16 (3.0%) in ATM, 16 (3.0%) in BRCA2, 8 (1.5%) in SPINK1, 2 (0.4%) in BRCA1, and so on. The most common genomic alterations were KRAS (89.5%), TP53 (77.5%), CDKN2A (30.8%), and SMAD4 (27.6%). Patients with co-mutation of 3- 4 driver genes above-mentioned accounted for 37.7%, which was significantly more prevalent in metastasis than primary (44.1% vs 35.3%, P<0.05). The most frequently mutated KRAS codon was G12D (37.4%), the second was G12V (29.4%). In addition, KRAS is mutually exclusive with BRAF and CTNNB1 mutations. BRCA1/2 and PALB2 mutations were detected in 6.9% of patients. The frequency of MSI-H was 0.4%. The median TMB was 3.36 muts/Mb, and 2.6% of the patients had TMB value greater than 10muts/Mb. Other drug-targeting genes included BRAF (2.6%) and ERBB2 (1.7%).
Conclusions
To our knowledge, this is the largest PACs cohort of genomic features in Chinese PAC patients. Germline mutations were detected in 11.1%, consistent with Western population. Approximately 8% of patients carrying actionable mutations may benefit from targeted therapies reported in clinical trials and case reports. The genomic profile study may provide information for targeted therapy or immunotherapy which will improve outcomes of Chinese PACs.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The Second Affiliated Hospital, College of Medicine, Zhejiang University.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.