| International Session（Symposium）3(JSGS・JSGE・JSH・JSGCS) |
| Fri. November 22nd 14:00 - 16:30 Room 2: Kobe International Exhibition Hall No.2 Building Hall (South) |
| Inter- and Intra-tumor Heterogeneity of Genetic Profiles and Microsatellite Instability Status in Patients with Gastric Cancers | |||
| Yosuke Hirotsu1, Hitoshi Mochizuki1,2, Masao Omata2,3 | |||
| 1Genome Analysis Center, Yamanashi Prefectural Central Hospital, 2Department of Gastroenterology, Yamanashi Prefectural Central Hospital, 3The University of Tokyo | |||
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| Background OPDIVO was launched in September 2017 for gastric cancers refractory to previous chemotherapy and KEYTRUDA in December 2018 for MSI-H. We have two options to treat advanced gastric cancer. We aim to study the genetic features linked to treatment strategies. Method A total of 726 tumor tissues from all organs including stomach, colon, pancreas, breast, lung, esophagus were subjected to IHC of MMR proteins (MLH1, MSH2, MSH6 and PMS2). Among those 726, 60 gastric tumors subjected to sequencing with in house gastric cancer panel, which targeting 58 significantly mutated genes and spanning 351,050 nt. Methylation of MLH1 promoter was examined by MSP-PCR. Results Of 60 patients with gastric cancers, 12 (20%) had deficient MMR (dMMR) tumors. Genetic profiles and MSI status were completely different in multiple gastric cancers. MLH1 promoter was methylated in MSI-H tumors. In two patients, cancer subpopulations of dMMR or proficient MMR were mixed. MSI status in tumor portions was concordant with the results of MMR staining. These results suggested the heterogeneity of genetic background influence on the treatment effect of immune-oncology. Conclusion Inter- and intra-tumor genetic heterogeneity was observed in both multiple and single gastric tumors. We had better conduct MSI analysis on all distinct tumor lesions to determine patients that will respond to immunotherapy. These ”switching” and ”mixing” genetic features would prompt us to consider the chemo-, molecular-, and immune-oncology treatments strategies. |
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Index Term 1: MSI Index Term 2: genome |
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