The Center for Applied Genomics has been at the forefront of research into the genetic causes of several types of cancers and tumors. We have led or co-led a number of key studies identifying risk factors for pediatric cancers, including neuroblastoma, infantile myofibromatosis, and others. We are actively collaborating with researchers at CHOP and elsewhere on translational studies aimed at developing individualized cancer treatments.

Neuroblastoma is a type of cancer most commonly found in children that affects the sympathetic nervous system (part of the nervous system that helps control our organs). It is often lethal. Our group has published a series of studies on the genetic causes of neuroblastoma, identifying several significant associations between neuroblastoma risk, including a region of chromosome 6 that was the first susceptibility site ever identified. We followed-up this finding by identifying a region on chromosome 2 on or near the BARD1 gene that has been found to regulate cell growth and tumor suppressants. We have also led several important studies identifying copy number variations (CNVs) as a potential cause of neuroblastoma and other cancers.

Infantile myofibromatosis (IM) is the most common fibrous tumor in infancy, usually resulting in a single lesion head and neck shortly after birth. We used whole-exome sequencing (WES) in members of nine families clinically diagnosed with a subtype of the disease, autosomal-dominant IM. We identified one of two disease-causing mutations in a gene called PDGFRB, and an IM-associated mutation in a gene called NOTCH3. We are pursuing PDGFRB and NOTCH pathways as opportunities to identify mutations in other genes that result in IM and a key to understanding the mechanisms of tumor growth and regression, and its targeted treatment.

Testicular cancer is the most common form of cancer in men between the ages of 15 and 34, but also peaks in infancy, as well as in men over the age of 60. We identified an area on chromosome 5 as a major risk factor for the disease, which was in the region of a gene called SPRY4. A specific copy of this gene is associated with a 40% greater chance of testicular cancer. Even more strikingly, we identified a region in chromosome 12 within a gene called KITLG. Patients with a specific form of the KITLG gene were much more likely to have testicular cancer – each copy of the gene-form increased risk of testicular cancer threefold. This represents one of the largest effect sizes reported in cancer.