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Research Seminar (24 Oct 2016)

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Research Seminar

Centre for Genomic Sciences

The Cancer Genome Atlas (TCGA) Project
and the Interaction of TP53 and NF-κB

Dr Zhong Chen

MD, PhD, Chief of Clinical Genomics, Head and Neck Surgery Branch,
NIDCD, NIH, Bethesda, Maryland, USA

24 October 2016 (Mon)
11:30 am – 12:30 pm


Seminar Room 1A, G/F

The Hong Kong Jockey Club Building for Interdisciplinary Research
5 Sassoon Road, Pokfulam, Hong Kong

 
Abstract:

The Cancer Genome Atlas (TCGA) Project was initiated about 10 years ago through a collaboration of National Institute of Health (NIH) and more than 20 institutes in US and Canada. TCGA has conducted genomic studies of 11, 000 human tissue samples from 33 major cancer types using different high throughput technologies, such as exome DNA, mRNA, or miRNA sequencing, and SNP, methylation, or protein arrays. These large scaled and integrated studies of TCGA project allow us to understand the landscape of major genetic and genomic alterations, revolutionize how cancer is classified, and identify new therapeutic targets. We have participated in the comprehensive genomic characterization of head and neck squamous cell carcinomas (HNSCC, Nature 2015), of which 279 tumor cases have been studied. We showed that smoking-related HNSCC demonstrated loss-of-function TP53 mutations, CDKN2A inactivation, and frequent copy number amplification of 3q26/28 and 11q13/22. Human papillomavirus associated tumors exhibited oncogene PIK3CA mutations and TRAF3 mutations or deletions. In addition, we have participated in the PanCan 12 project, that the datasets from 3527 human specimens cross 12 cancer types were integrated and analyzed (Cell 2014).  Consistent with the findings from TCGA project, recently our laboratory investigated how inflammatory cytokine TNF-α modulates the interactions of TP53 and NF-κB family members. Through integrated analysis of the data from ChIP-seq, microarray and other high throughput technologies, we observed that TNF-α mediated genome-wide redistribution of the cREL/p63/p73 and AP-1 interactome, to diminish TAp73 tumor suppressor function and reciprocally activate NF-κB and AP-1 gene programs implicated in malignancy (Oncogene, 2016)


About the Speaker:

Dr Zhong Chen received her medical degree from Beijing Medical University, and a PhD degree from University of Rochester, NY, USA. Dr Chen’s research traverses several diverse disciplines relating to translational oncology and genomics, including cell and molecular biology, gene expression and transcriptional regulation, high throughput sequencing, functional genomics, animal tumor models, preclinical and clinical investigation, and new drug testing. She has participated in several pre-clinical investigations and phase 0/I clinical trials testing novel anti-cancer therapies targeting PI3K, MEK, CK2, heat shock protein, EGFR, and NF-κB pathways.

 

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