Survey
* Your assessment is very important for improving the work of artificial intelligence, which forms the content of this project
Download Presentation Slides
Document related concepts
no text concepts found
Transcript
Cancer genetics - the case of hepatocellular carcinoma Daniel Ho Department of Pathology HKU Central dogma of biology •Copy number alterations •Mutations •Structural variations •Expressional alterations •Epigenetic alerations •Gain/loss of function •Degradation https://www.ncbi.nlm.nih.gov/Class/MLACourse/Modules/MolBioReview/central_dogma.html Somatic vs germline alterations https://www.ncbi.nlm.nih.gov/books/NBK21894/ What are oncogenes and proto-oncogenes? •Oncogenes have the potential to cause tumor formation •Proto-oncogenes are normal genes by default but acquire malignant functions when mutated or upregulated •Typically dominant https://en.wikipedia.org/wiki/Oncogene What are fusion genes? Philadelphia chromosome •Consequence of chromosomal translocation •Parts of chr 9 and 22 exchanged •Formation of BCR-ABL fusion gene by joining BCR (22q11) and ABL (9q34) •Commonly found in leukemia Detection by FISH What are tumor suppressor genes? •Gatekeeper for abnormal cellular events •Knudson two-hit hypothesis •Typically recessive •Dominant negative or haploinsufficiency http://uvmgg.wikia.com/wiki/Tumor_suppressor Cancer – inactive tumor suppressor and active oncogene http://cisncancer.org/research/what_we_know/advances/oncogenes.html What are copy number alterations? Microarray NGS Copy number alterations in HCC Recurrently amplified and deleted genes in HCC Shibata, T. & Aburatani, H. (2014) Exploration of liver cancer genomes Nat. Rev. Gastroenterol. Hepatol. doi:10.1038/nrgastro.2014.6 What are mutations? http://evolution.berkeley.edu/evolibrary/article/evo_20 http://www.vce.bioninja.com.au/aos-3-heredity/molecular-genetics/mutations.html What are structural variaions? http://www.vce.bioninja.com.au/aos-3-heredity/molecular-genetics/mutations.html Genomic alterations in HCC Totoki, et al. Nature Genetics. 2014 Genomic alterations in HCC Schulze, et al. Nature Genetics. 2015 Druggable mutations in HCC Ho, Chan, et al. Gut. doi:10.1136/gutjnl-2016-312734 Druggable mutations in HCC Ho, Chan, et al. Gut. doi:10.1136/gutjnl-2016-312734 Druggable mutations in HCC Ho, Chan, et al. Gut. doi:10.1136/gutjnl-2016-312734 Druggable mutations in HCC Ho, Chan, et al. Gut. doi:10.1136/gutjnl-2016-312734 Druggable mutations in HCC Ho, Chan, et al. Gut. doi:10.1136/gutjnl-2016-312734 Viral integration in cancers Chen, et al. Cancers. 2014. HBV viral integration in HCC Sung, et al. Nature Genetics. 2012 HBV viral integration in HCC Chiu, Wong , et al. Journal of Hepatology. 2016 64, 1256-1264. DOI: (10.1016/j.jhep.2016.02.005) HBV viral integration in HCC Chiu, Wong , et al. Journal of Hepatology. 2016 64, 1256-1264. DOI: (10.1016/j.jhep.2016.02.005) HBV viral integration in HCC Chiu, Wong , et al. Journal of Hepatology. 2016 64, 1256-1264. DOI: (10.1016/j.jhep.2016.02.005) Strategy for viral integration detection Human Chimeric genomic fragment (Soft-clipped reads) HBV Human Workflow of Virus-Clip Ho, et al. Oncotarget. 2015 Performance comparison of Virus-Clip with other existing tools Ho, et al. Oncotarget. 2015 Detecting transcriptomic alterations by differential gene expression analysis Ho, et al. Front Med. 2015 Molecular pathogenesis of HCC Multi-step accumulation of oncogenic alterations at multiple levels Ho, et al. Liver Cancer. 2016
Related documents