By Sridhar Hannenhalli, NIH USA

Abstact 

While mutations, specifically those affecting protein-coding genes, have been a major focus of cancer research, they do not explain oncogenesis, metastasis, and therapy response entirely, and epigenetic plasticity is emerging as a potent complementary mechanism. Stochastic gene expression variability is intimately linked to cellular plasticity, which while being an integral part of development and stress response, is also linked to cancer and presents a major challenge for cancer therapy. I will present our recent work showing existence of transcriptionally distinct subpopulation of healthy pancreatic acinar cells exhibiting features of ductal-acinar progenitor state pancreatic ductal adenocarcinoma. Parallels between development and cancer has long been noted and recent works have identified activation of developmental programs in cancer. I will briefly summarize our recent works showing (1) a novel developing melanoblast cell state associated with metastasis and therapy response in melanoma and (2) a broad misappropriation of developmental splicing programs by cancer. Time permitting, I will summarize our recent attempts to characterize non-coding mutations during evolution and in cancer.