Abstract 5298
Background
Gastric cancer (GC) is a leading cause of cancer deaths. Tumor staging has been conceived as the best predictor of patient survival. Nevertheless, TNM classification has limited power to fully reflect the complicated progression events. Prognosis varies from individual to individual even though the two patients stay in a similar tumor stage, therefore the molecular biology of the individual tumor might be the key point to better understand the nature of GC. The identification of somatic mutations (SM) has the potential to offer diagnostic and prognostic information. The present study is focusing on implementation of clinical exome sequencing for SM identification.
Methods
18 gastric cancer specimens and 18 corresponding adjacent normal gastric specimens were obtained from GC patients with stages from Ia to IV. Paired-ended sequencing was performed using Trusight one sequencing panel (Illumina) on a NEXTSEQ500 platform. 94,5% of the target regions were represented with an average sequencing depth of 20-fold. A somatic variant list was generated for each patient by using MuTect.
Results
Tumor and normal library targeted 4,813 genes associated with known clinical phenotypes were sequenced with mean coverage of 99x. Mean number of detected variations was 7613 per sample. After MuTect filtration the amount of SM was varied from 2 to 414 per sample. We found 692 SM: 5 pathogenic mutations in TP53, ARID1A and HER2 genes, 40 were described in COSMIC and dbSNP database, the rest were novel mutations. By the time of 2 years follow-up, 5 patients (27.8%) died, all of them had intermediate grade adenocarcinoma. Importantly, all of them had dramatic number of SM (from 37 to 414). At the operation moment 3 of them had III stage, 2 of them had 1b and IIa stages. For patients with overall survival (OS) > 2 years the number of SM increases with disease stage: I-II stage from 2 to 12, III stage – from 2 to 20, IV stage – from 12 to 43. For patients with OS < 2 years the number of SM was high nevertheless stage.
Conclusions
We found more than 600 novel mutations, from them 18 mutations were localized in genes previously associated with gastric cancer pathogenesis. In the current moment of the investigation patients with high level of SM have unfavorable prognosis (OS less than 2 year) regardless of stage.
Clinical trial identification
Legal entity responsible for the study
Research Center of Medical Genetics, Moscow, Russia.
Funding
State assignment of FASO Russia.
Editorial Acknowledgement
Disclosure
All authors have declared no conflicts of interest.
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