Abstract 998P
Background
The approval of ICIs for HCC has changed the treatment landscape of HCC, which is the fourth most common and the second lethal malignancy in China. But ICIs have also been linked to the possibility of accelerating disease progression. Previous reports have indicated MDM2/MDM4 amplifications (amp), EGFR alterations, DNMT3A alterations, CDKN2A/B gene loss and amp of 11q13 region containing CCND1, FGF3, FGF4 and FGF19 are biomarkers associated with HP in a variety of cancers. Hence, the study of those genes in HCC might be useful in avoiding adverse effect.
Methods
Targeted deep sequencing with 450 cancer-associated genes was performed on formalin-fixed, paraffin-embedded (FFPE) tumor tissues and matching blood samples that collected from a cohort of 1292 Chinese HCC patients. The HP-related genomic alterations such as MDM2/MDM4 amp, EGFR alterations, DNMT3A alterations, CDKN2A/B gene loss and 11q13 amplification were subsequently analyzed.
Results
A total of 1292 HCC patients (male=1121, female=171) was included in this study, of which 202 (15.6%) patients presented HP-related gene alterations. Among them, MDM2/MDM4 amp, EGFR alterations, DNMT3A alterations, CDKN2A/B gene loss and 11q13 amp were identified in 6 (0.46%), 16 (1.24%), 13 (1.01%), 58 (4.49%) and 118 (9.13%) patients respectively. The median tumor mutational burden was 6.3 muts/Mb (ranged from 0-554.5 muts/Mb) and the median age was 55 yrs (ranged from 7-87 yrs). DNMT3A alterations were associated with significantly higher age than the wild-type cases (median age: 60 yrs vs 55 yrs; P= 0.0096). In the 11q13 amplification subgroup, the frequency of patients with stage III-IV was significantly higher than that with stage I-II (36.2% vs 19.4%, P= 0.0048).
Conclusions
To our knowledge, this was the largest cohort studying the mutational landscape of biomarkers associated with HP in response to ICIs in Chinese HCC patients. The high incidence of 11q13 amplification and CDKN2A/B gene loss was observed in the cohort. Therefore, the application of comprehensive genomic profiling companion diagnosis might be necessary in guiding the regimen and ICI treatments.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Hunan Provincial People's Hospital.
Funding
Has not received any funding.
Disclosure
H. Qing, Y. Shaohua, W. Weifeng: Full/Part-time employment: OrigiMed. All other authors have declared no conflicts of interest.