Final year project presentation_HKPU_Shiyi YIN_23NOV2015

Title:

A comparative study into the genetic relationship of spontaneous hepatocellular carcinoma and hepatitis B virus induced hepatocellular carcinoma using bioinformatics analyses

Abstract:

Forward genetics is a widely applied method to screen for candidate malignant mutations, these research generate numerous amount of genetic data in mouse model. This study analyzed data from two transposon-based mouse models to further elucidate the genetic mechanisms associated with spontaneous hepatocellular carcinoma (HCC) and hepatitis B virus (HBV) induced hepatocellular carcinoma. There were 87 common genes identified in both types of mouse HCC models. Amongst these 87 genes, Zinc finger and BTB domain containing 20 (Zbtb20) and dihydropyrimidine dehydrogenase (Dpyd) occurred at high frequency regardless HCC mouse model types. This study also processed 87 common genes between two mouse HCC models using TCGA (The Cancer Genome Atlas) database to translate mouse experimental findings into clinical significance. Lysosomal trafficking regulator (LYST), WW domain containing E3 ubiquitin protein ligase 1 (WWP1), ash1 (absent, small, or homeotic)-like (Drosophila) (ASH1L), pogo transposable element with ZNF domain (POGZ) and regulator of microtubule dynamics 1 (RMDN1) were frequently mutated in human HCC samples (n=193). Gain of copy number and mRNA overexpression patterns of these genes in clinical samples suggested that these genes reassemble pro-oncogene. Amongst them, frequency of WWP1 mutation occurrence also varied significantly across ethnicity with two fold increase in Asian population (n=40) comparing to non-Asian (n=115). Ingenuity Pathway Analysis (IPA) highlighted hypoxia signaling pathway (P=7.38E-06) amongst common genes indicating its importance role in both types of HCC tumorigenesis. Based on above results, Dpyd and Zbtb20 were hypothesized to be candidate earlier drivers in both types of mouse HCC models. RMDN1, WWP1, ASH1L and POGZ were hypothesized to be candidate earlier drivers in both types of human HCC tumorigenesis. Future research proposals are suggested to validate these hypotheses.

Acknowledgement

Special thanks to supervisor of this study, Dr. Vincent W. KENG, for his patient
guidance, enthusiastic encouragement and useful critiques of this research work

List of other contributors:
Dr. Vincent KENG’s Team, Hong Kong Polytechnic University, HK
Miss. Amy P. CHIU
Ms. Lilian H. LO
Miss. Karen K. CHAN
Ms. Xiaoxiao LI
(Former members)
Mr. Kit F. IU
Miss. Yuzhu CUI
Ms. Weiyu ZHANG
Dr. David A. LARGAESPADA’s Team, University of Minnesota, MN, US
Dr. Branden S. Moriarity
Ms. Barbara R. Tschida
Dr. Irene O. NG’s Team, University of Hong Kong, HK
Dr. Carmen C. WONG
Dr. Daniel W. Ho
Dr. Sheng CHEN’s Team, Hong Kong Polytechnic University, HK
Mr. Renjie ZHOU

Video info:
Clean shot no cut or any editing (this has always been my style)
Camera borrowed from Ms. Siu Wai WAN (thanks)
Camera ladies are Ms. Ning CHOW & Ms. Kwan Wun TSANG (thanks)

Gene list mentioned in this video is available upon request via email to shiyi.yin@case.edu