A fundamental goal of human genetics is to decipher the relationship between genotype and phenotype.
Cancer is defined as a disease comprising a heritable genetic component that confers cancer predisposition
and an acquired (somatic) component where disease is driven by an accumulation of genetic mutations
leading to ever increasing deregulation of normal cellular functions. Population based genome wide
association studies (GWAS) and whole genome sequencing (WGS) analyses have identified thousands of
germline risk variants for ovarian cancer and somatic non-coding mutations involved in ovarian cancer
development. Identifying genomic regions where there are interactions between germline and somatic variants
may enable us to identify the critical drivers of disease. We have established an end-to-end pipeline that can
efficiently evaluate the functional significance of thousands of genetic variants in disease at once. We have
also established ex-vivo models of fallopian tube secretary epithelial cells (precursors of ovarian cancer) and in
vitro 3D models of chemoresistant ovarian cancer. In this proposal, we plan to address provocative question #3
“Do genetic interactions between germline variations and somatic mutations contribute to differences in tumor
evolution or response to therapy?” with the following specific aims: (1) Use computational approaches, to
identify genomic regions where germline and somatic genetic variants converge to indicate shared target
genes and regulatory networks driving ovarian cancer development; (2) Use chromosome conformation
capture assays to validate interactions between regulatory targets and their target genes; (3) Use
CRISPR/Cas9 screens to establish the functional significance of germline-somatic interacting regions in
ovarian cancer development.
If you are accessing this page during weekend or evening hours, the database may currently be offline for maintenance and should operational within a few hours. Otherwise, we have been notified of this error and will be addressing it immediately.
Please contact us
if this error persists.
We apologize for the inconvenience.
- The DCCPS Team.