Abstract 107P
Background
Hepatobiliary cancer (HBC) is a type of aggressive disease with poor prognosis and patients with advanced HBC have limited therapeutic options. Genomic characterization for cancer patients by next-generation sequencing has become an effective approach to facilitate the development of target therapy. IDH1 and DNA damage repair genes (DDR) mutations have been identified in HBC patients and they usually indicate a longer overall survival (OS). Here, we for the first time we know revealed the genomic feature of co-mutation patterns of IDH1 and DDR genes in HBC patients in both Western and Chinese populations and compared OS in different mutation pattern.
Methods
Tumor tissue and blood were collected from 499 HBC patients and then analyzed by AcornMed Biotechnology NGS-based assay for 808 genes panel or whole exome sequencing. Data of 769 European HBC patients from cBioPortal were used.
Results
The IDH1 mutation frequency in Chinese and Western cohort were 3.4% and 5.2% （P > 0.05）while DDR gene (88 core genes) were 22.6% and 17.6% (P < 0.05). RAD54L and BRCA1 mutation frequency in IDH1 mutated group were higher while ADRID1A was lower compared with IDH1 wild type group in Chinese cohort, but were not significant. In Western cohort, we observed ARID1A, BRCA1 and ATM mutated more frequently in IDH1 mutated group while only ARID1A was still significant after multiple testing (P < 0.01). Moreover, HBC patients with co-mutated IDH1 and DDR genes have the longest OS (median 52.7 months) while patients without mutation of these genes have shortest OS (median: 27.9 months) among all IDH1 and DDR genes mutation patterns, but didn't reach statistical difference level. Table: 107P
OS of different IDH1 and DDR mutation pattern
| Mutation Pattern | n | Events | Median (months) | 0.95LCL (months) | 0.95UCL (months) |
| co_mutate | 13 | 7 | 52.9 | 21.8 | NA |
| co_wild type | 289 | 181 | 27.9 | 24.4 | 38 |
| IDH1_mutate_only | 26 | 15 | 46.8 | 21.7 | NA |
| DDR_genes_mutate_only | 75 | 52 | 37.9 | 23.0 | 53.5 |
| IDH1_wild type | 364 | 233 | 28.7 | 25.2 | 38.4 |
| DDR_genes_wild type | 315 | 196 | 28.6 | 24.4 | 38 |
Conclusions
Our study revealed different mutation pattern of DDR genes in Western and Chinese HBC populations and identified a more favorable OS in IDH1 and DDR genes co-mutated group, providing new insight for investigation of the target therapy for HBC patients.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
F. Yang, T. Yang, F. Lou, S. Cao, H. Wang: Financial Interests, Personal, Full or part-time Employment: AcornMed Biotechnology Co., Ltd. All authors have declared no conflicts of interest.