Integrating Epidemiologic and Genomic Data to Elucidate the Genetic Overlap Between Congenital Anomalies and Pediatric Cancer

ABSTRACT

In the United States, cancer remains the leading cause of death by disease in those 90,000 individuals; and 3) the GOBACK Registry Linkage Birth Cohort, which

includes population-based data on >25 million live births. In Aim 1, we will analyze an expanded population-

based cohort of >25 million children to identify new CA-PC patterns and confirm previously reported patterns.

In Aim 2, we will analyze germline whole-genome sequencing (WGS) data from 2,000 children with both

congenital anomalies and pediatric cancer and over 20,000 children with either congenital anomalies or

pediatric cancer to identify novel pleiotropic genes harboring rare, pathogenic variants responsible for specific

CA-PC patterns. In Aim 3, we will describe the landscape of somatic alterations in pediatric cancers that result

from pathogenic CA-PC variants through the analysis of tumor-normal WGS and RNA-Seq data in 2,000

children. This work will generate novel insights into cancer predisposition and subsequently lead to improved

care for children with congenital anomalies, who comprise 120,000 births every year in the United States. In

addition, insights into cancer development among at-risk populations could provide clinical utility (e.g., genetic

counseling or therapeutic targets) for children and adults with cancer in the general population.