The Center for Applied Genomics has been at the forefront of research into the genetic causes of neuroblastoma and testicular cancer and has had a major impact on our understanding of these diseases.


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.

In 2008, our group published the first of three important papers on the genetic causes of neuroblastoma. We performed a genome-wide association study (GWAS) comparing the genomes of 1032 patients and 2043 controls. We found a significant association between neuroblastoma and a region of chromosome 6. This was the first neuroblastoma susceptibility site ever identified. John Maris was first author on the paper, which was published in the New England Journal of Medicine.

In 2009, we followed-up this finding by publishing another GWAS that focused on a 397-person high-risk subset of the neuroblastoma group. We identified a region on chromosome 2 on or near the BARD1 gene, which has been found to regulate cell growth and tumor suppressants. These data show that a common variation in the BARD1 gene contributes to aggressive neuroblastoma – the most clinically important form of the disease. Mario Capasso was first author on this paper study that was published in the journal Nature Genetics.

In 2009, we contributed another study identifying copy number variations (CNVs) as a potential cause of neuroblastoma. CNVS are segments of DNA consisting of deleted, duplicated, or rearranged genetic material. We identified a CNV on chromosome 1 that associated with the disorder. It behaved similarly to a class of genes known as neuroblastoma breakpoint family (NBPF) genes and was thus implicated as a previously unknown member of the neuroblastoma breakpoint family gene. The study was the first germline CNV study in any cancer. Sharon Diskin was first author on this paper, which was published in the journal Nature.

Testicular Cancer

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. In 2009, we published the results of a genome-wide associated study that examined the genomes of 227 patients with testicular germ cell tumors and 919 controls. 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. Peter Kanetsky was first author on this paper that was published in Nature Genetics.