Abstract 752: Unveiling Korean cancer-associated gene using large-size cancer germline mutation data
Authors: Yuh Gangpyo , Song Seulki , Cho Eunju , Kim Miso , Kim Hyery , Koh Youngil , Park Jookyung , Yoon Sungsoo , Lee Sehoon 
Published: June 2022

Abstract
We are focusing on the germline mutation data to understand the possible cancer-causing gene mutation that has a chance of inheritability to the next generation. Cancer genomics has been already widely studied around the world in a pan-cancer manner. But we found that the majority of the ethnicity of the data sequenced is mainly the US and European origin. For the Korean cancer cohort, it is clear that the lack of sample size was the bottleneck for ethnicity-specific studies. It is necessary that there is a limited number of the study contribute to the knowledge that Korean specifically applicated to explore the possible association between germline mutation and cancer occurrences. The objective of this study is to discover the Korean-specific candidate genes that associate with the tumor.Our study collected around 3000 Korean-specific samples consisting of various cancer types and normal control. We also gathered normal control samples for 354 Super-Normal (tumor-free, age &lt; 65, med-checked) samples, and 1094 Korean normal (U1K) samples. Whole Exome Sequencing has been applied for every sample except U1K cohort that has already been whole genome sequenced. Genome-Wide Association Test (GWAS) has been executed between Korean-specific cancer patients and Korean normal samples. The study has been dichotomously analyzed, common variants are studied by GWAS fashion, and the rare variants are studied by gene-level aggregated fashion. Not only statistically, but also functionally we make use of the knowledge that Nonsense Mediated Decay (NMD) information to break the limitation of the unexplained gene mutation that does not follow the Central Dogma. Clinical validation data is also utilized. In a clinical aspect, we validated the dataset with a Clinvar and decided whether the mutation has a piece of clinical evidence or not.By conducting a series of studies, we have successfully found that some candidate genes which are known for DNA binding genes including PABPC1, PABPC3, and ZNF717 were significantly associated. Indeed, a cell division cycle associated gene like CDC27 also represents a significant association with cancer phenotype. Furthermore, ATXN3, SEPT2, PCMTD1 mutation is observed more in the cancer cohort. We are performing comparison studies to further elucidate which ethnic group represents more gene mutation on different cancer types.In summary, we propose the method that presents the possible germline mutation that is associated with phenotype by various factors, and also proposed Korean-specific candidate genes that associate with cancer.
Citation Format: Gangpyo Yuh, Seulki Song, Eunju Cho, Miso Kim, Hyery Kim, Youngil Koh, Jookyung Park, Sungsoo Yoon, Sehoon Lee. Unveiling Korean cancer-associated gene using large-size cancer germline mutation data [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 752.