Faculty

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Subhajyoti De
Assistant Professor
Department: Department of Pathology & Laboratory Medicine
Phone: 1.7322358558
Email: subhajyoti.de@rutgers.edu
Robert Wood Johnson Medical School
The Cancer Institute of NJ, Room 4558
195 Little Albany Street
New Brunswick, NJ 08901
Key Words: Cancer genomics, genome evolution, algorithms, systems biology, precision medicine
Lab Site URL

Genomic instability in cancer

We have recently shown that nuclear localization, DNA replication timing and genomic context play critical roles in shaping the landscape of amplifications, deletions, point mutations, and loss of heterozygosity in cancer genomes. Our findings provide insights into different mutagenic processes, and has implications for identifying driver and passenger mutations in the cancer genomes.

Regulatory alterations in cancer

Genomic and epigenetic abnormalities leading to deregulated oncogenic pathways are found in many types of cancer. We found a novel signature of accelerated somatic evolution in many types of cancer, which is marked by significant excess of somatic mutations in a genomic region in multiple cancer genomes. The signature is frequently associated with non-coding regulatory changes leading to deregulation of oncogenic pathways and adverse clinical outcome. In another project, we found that epigenetic heterogeneity in B cell lymphoma is increases markedly with disease aggressiveness, and is associated with unfavorable clinical outcome. Our findings provide mechanistic insights into the biology of regulatory alterations in cancer.

Evolutionary dynamics of cancer

We use a combination of computational, genomics, and mathematical tools to study evolutionary dynamics of cancer, including order of mutation events and emergence of resistance. We found that not only the driver mutations are important, but the order in which they arise is also important. Although there is no obligatory order of events, we found that loss of PTEN is the most common first event and is associated with basal-like subtype, whereas in the majority of luminal tumors, mutation of TP53 occurs first and mutant PIK3CA is rarely detected. Furthermore, resistant mutations are often present at low frequency during treatment. Our results have important implications for the design of chemopreventive and therapeutic interventions in this high-risk patient population.

Somatic mutations in benign human tissues

From the fertilization of an egg until the death of an individual, somatic cells can accumulate genetic changes, such that cells from different tissues or even within the same tissue differ genetically. The presence of multiple cell clones with distinct genotypes in the same individual is referred to as 'somatic mosaicism'. Many endogenous factors such as mobile elements, DNA polymerase slippage, DNA double-strand break, inefficient DNA repair, unbalanced chromosomal segregation and some exogenous factors such as nicotine and UV exposure can contribute to the generation of somatic mutations, thereby leading to somatic mosaicism. Such changes can potentially affect the epigenetic patterns and levels of gene expression, and ultimately the phenotypes of cells. Although recent studies suggest that somatic mosaicism is widespread during normal development and aging, its implications for heightened disease risks are incompletely understood. We found that somatic mutations in benign somatic tissues carry signatures of relaxed purifying selection.

Publications