GENOMIC INSTABILITY AND CANCER GENETICS PROGRAM PROJECT SUMMARY/ABSTRACT The Genomic Instability and Cancer Genetics (GICG) Program is organized around the central concepts that cancer results from the accumulation of genomic alterations, and that well-defined descriptions of DNA repair mechanisms, cancer genomes, and gene expression landscapes can reveal the vulnerability of cancer to interventions. The overall goal is to determine how cells maintain the integrity of their genomes, define the landscapes of cancer genomes, and facilitate identification of biomarkers and therapeutic targets. The GICG Program is composed of a highly qualified team of 44 members of diverse and complementary expertise from 19 Departments, 7 Schools, and 2 Universities. Our research is funded by a total of $11.2 million annual direct funding, including $8.6 million cancer-relevant funding ($3 million annual direct funds from NCI), 22 fully-cancer focused and NIH R01 equivalent research grants from 17 different and independent PD/PIs, and 11 multi-PI awards. Productivity and collaboration within GICG is evident from the significantly increased cancer-focused publications (586, up from 388 in 2004-2010), 30% collaborative publications (up from 25% in 2004-2010) including those that are 17% intra- and 24% inter-programmatic (up from 9.3% and 20% in 2004-2010), 54% inter-institutional collaborative publications, and 28% of the publications are in top tier journals. Achievements toward the scientific goals are exemplified by the demonstration of a distinct role of BRCA1- PALB2 interaction in supporting conserved homologous combinational DNA repair and suppressing mutagenic DNA single strand annealing, identification that the Pif1 DNA helicase overcomes replication fork blocks at G4-rich regions, mechanistic elucidation of the gain-of-function p53 mutations in the regulation of cancer metabolism and metastasis, discovery of two subtypes of oncocytomas with distinct mutational signatures, and the discovery of increased mutation burden at the nuclear peripheral lamina chromosome domains due to genome wide DNA repair heterogeneity. Translation and inter-programmatic interaction are reflected by the contribution of GICG to the genomic analysis of tumors with the application of state-of-the- art cancer genomic approaches as an integrated part of our clinical practice of Precision Medicine, new clinical trials based on the understanding of genomic instability and cancer mutation burden, and laboratory inquiries of new hypotheses emanating from the Clinical Investigations and Precision Therapeutics (CIPT) Program.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Center Core Grants (P30)
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Subcommittee I - Transistion to Independence (NCI)
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Rbhs -Cancer Institute of New Jersey
New Brunswick
United States
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George, Blessy; Joy, Melanie S; Aleksunes, Lauren M (2018) Urinary protein biomarkers of kidney injury in patients receiving cisplatin chemotherapy. Exp Biol Med (Maywood) 243:272-282
Paratala, Bhavna S; Chung, Jon H; Williams, Casey B et al. (2018) RET rearrangements are actionable alterations in breast cancer. Nat Commun 9:4821
Jian-Yu E; Graber, Judith M; Lu, Shou-En et al. (2018) Effect of Metformin and Statin Use on Survival in Pancreatic Cancer Patients: a Systematic Literature Review and Meta-analysis. Curr Med Chem 25:2595-2607
Moloughney, Joseph G; Vega-Cotto, Nicole M; Liu, Sharon et al. (2018) mTORC2 modulates the amplitude and duration of GFAT1 Ser-243 phosphorylation to maintain flux through the hexosamine pathway during starvation. J Biol Chem 293:16464-16478
Zhu, Sining; Jin, Juan; Gokhale, Samantha et al. (2018) Genetic Alterations of TRAF Proteins in Human Cancers. Front Immunol 9:2111
Perekatt, Ansu O; Shah, Pooja P; Cheung, Shannon et al. (2018) SMAD4 Suppresses WNT-Driven Dedifferentiation and Oncogenesis in the Differentiated Gut Epithelium. Cancer Res 78:4878-4890
Hadigol, Mohammad; Khiabanian, Hossein (2018) MERIT reveals the impact of genomic context on sequencing error rate in ultra-deep applications. BMC Bioinformatics 19:219
Llanos, Adana A M; Tsui, Jennifer; Rotter, David et al. (2018) Factors associated with high-risk human papillomavirus test utilization and infection: a population-based study of uninsured and underinsured women. BMC Womens Health 18:162
Shih, Weichung Joe; Lin, Yong (2018) Relative efficiency of precision medicine designs for clinical trials with predictive biomarkers. Stat Med 37:687-709
Severson, Eric A; Riedlinger, Gregory M; Connelly, Caitlin F et al. (2018) Detection of clonal hematopoiesis of indeterminate potential in clinical sequencing of solid tumor specimens. Blood 131:2501-2505

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