Abstract 1963P
Background
Mutations in GNAQ and GNA11 are early events that promote cell proliferation, and these mutations are sensitive to MAPK kinase, PKC, and AKT inhibitors. Uveal melanoma is characterized by GNAQ/GNA11 mutations, leading to the use of PKC inhibitors as a rational treatment strategy and encouraging clinical activity has been noted recently. The application of PKC inhibitors in other cancers requires a comprehensive understanding of the prevalence and types of GNAQ/GNA11 mutations. Herein, we systematically analyzed our large-scale data to explore the frequency and mutation spectrum of GNAQ/GNA11 in Chinese cancer patients.
Methods
We screened genomic profiling results based on pan-cancer panel (containing GNAQ/GNA11) of tissue and/or plasma samples from 11,111 patients spanning 7 cancer types: melanoma (n=117), glioma (n=3401), lung (n=4348), gastric (n=723), colorectal (n=1149), liver (n=942) and bile duct cancer (n=431).
Results
Of the 11,111 patients screened, we observed 117 patients with GNAQ/GNA11 mutations, revealing an overall prevalence of 1.05%. Approximately, 0.68% harbored GNAQ mutations and 0.4% had GNA11 mutations. Interestingly, GNAQ or GNA11 mutations were mutually exclusive, with only 2 (1.7%) out of 117 mutations occurring simultaneously. Mutation rate was 9.4% (11/117), 1.57% (18/1149), 1.27% (12/942), 0.91% (31/3401), 0.9% (39/4348), 0.7% (3/431), 0.41% (3/723), in melanoma, colorectal, liver, glioma, lung, bile duct cancer and gastric cancer, respectively. The most common mutations of protein change was p.Thr96Ser (20.5%), followed by p.Tyr101* (14.5%) and p.Lys322Asn (2.6%), which mainly occurred in exon 2 (2/7) and exon7 (7/7). Additionally, co-mutations in TP53 (72, 62%), CREBBP (34, 29%), FAT3 (34, 29%), KMT2D (33, 28%), NF1 (32, 28%), APC (31, 27%), LRP1B (31, 27%) and KMT2C (30, 26%) were observed.
Conclusions
Our study provides a comprehensive view of GNAQ/GNA11 mutations in Chinese cancer patients. Further investigation is required to determine whether PKC inhibitor might offer therapeutic benefits.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Inner Mongolia People's Hospital.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.