Affiliation:
1. Department of Pathology, Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School Nanjing China
2. The Comprehensive Cancer Centre of Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School and Clinical Cancer Institute of Nanjing University Nanjing China
3. Shanghai OrigiMed Co., Ltd Shanghai China
Abstract
AbstractBackground and AimGastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor with high prevalence of KIT and PDGFRA mutations. Few effective treatments can be exploited in imatinib or sunitinib resistant cases. While in immunotherapy, application of the highly individualized cancer neoantigen vaccines is hampered due to high economic and time cost. In this study we identified the most frequent mutation in Chinese GIST patients and predicted candidate neopeptide by next generation sequencing (NGS).MethodsTumor tissues and matched blood samples of 116 Chinese GIST patients were collected. Genomic profile was detected through NGS, and 450 cancer genes were deeply sequenced. KIT mutations were identified, and long peptides containing the mutation were queried in NetMHCpan 4.0 tools to predict MHC class I binding of mutant peptides.ResultsThe most frequent mutated genes in detected GIST patients were KIT (81.9%, 95/116), CDKN2A (18.97%, 22/116), and CDKN2B (15.52%, 18/116) in this cohort. The most common mutation of KIT was A502_Y503 duplication (15.93%, 18/113) in exon 9. Among the 116 cases, 103 were HLA I genotyped, and 101 were HLA II genotyped. In total, 16 samples with the mutation of KIT p.A502_Y503dup were identified to produce neoantigens with qualified HLA affinity.ConclusionsKIT hotspot mutation (p.A502_Y503dup) has the highest incidence, which may further eliminate the need for whole genome sequencing and patient‐specific neoantigen prediction and synthesis. Therefore, for those carrying such mutation, accounting for around 16% of Chinese GIST patients and are usually less sensitive to imatinib, effective immunotherapies are in prospect.
Funder
National Natural Science Foundation of China
Jiangsu Provincial Key Research and Development Program
Natural Science Foundation of Jiangsu Province
Subject
Gastroenterology,Hepatology