Dr Christine Chio starts her own lab as an Assistant Professor at Columbia University!
Dr Michael Feigin published his work on recurrent non-coding mutations in PDAC!
Large-scale exome sequencing efforts have revealed genes and pathways important for cancer progression. However, the exome comprises less than 2% of the human genome and whole-genome sequencing (WGS) analyses have revealed tumors often carry thousands of somatic mutations per genome, the vast majority of which are located in noncoding regions and are completely uncharacterized. To detect somatic noncoding mutations (NCMs) in pancreatic cancer (PDA), I co-developed a computational pipeline to analyze WGS data of 308 PDA tumors. To discriminate amongst the thousands of identified NCMs, we developed GECCO (Genomic Enrichment Computational Clustering Operation) to identify candidate NCMs that drive differential gene expression. Using GECCO, we identified novel recurrent mutations and interrogated expression data from matched tumors to find several variants associated with changes in mRNA levels. We found significant differential expression of 16 genes associated with NCMs, and reveal two (PTPRN2, SLC12A8) with previously unidentified clinical relevance in PDA. Pathway analysis of the genes associated with recurrent NCMs identified known and novel PDA pathways. Furthermore, we found enrichment for mutations in specific regulatory regions, suggesting that NCMs may be acted upon by selection during tumor formation. Our analysis provides a model for tumor evolution via the formation and selection for alterations in noncoding regulatory elements of specific genes as a means of control over specific biological pathways.
Tuveson lab at the NYC Science March
Sat, Apr 22, 2017
Dr. Abram Handly-Santana successfully defended his PhD thesis
Abram Handly-Santana was the first graduate student to join the Tuveson lab soon after our arrival at Cold Spring Harbor lab. Abram was part of the Watson School of Biological Sciences program – CSHL’s own graduate school. His work focused on the heterogeneity of the non-cancerous fibroblasts in pancreatic cancer and their role in supporting and restraining the growth of tumor cells. You can find out more about his exciting work in his paper or the recent CSHL press release.
NRF2 Promotes Tumor Maintenance by Modulating mRNA Translation in Pancreatic Cancer
Chio et al., Cell. 2016 Aug 11;166(4):963-76. doi: 10.1016/j.cell.2016.06.056. Epub 2016 Jul 28.
Christine Chio recently published her paper in Cell on the role of the transcription factor NRF2 in regulating protein translation in pancreatic cancer.
You can find out more about her work and the field of redox here: