Scripps Translational Science Institute Contributes to Discovery of Cancer Gene

Scripps Translational Science Institute Contributes to Discovery of Predisposition Gene for Childhood Cancer

SAN DIEGO – Researchers at Scripps Translational Science Institute (STSI) have contributed to a major genetic breakthrough – the discovery of a gene responsible for the majority of inherited cases of a common childhood cancer. The finding was reported online Aug. 24 in Nature. The finding promises to provide a springboard for developing new therapeutic strategies.

Neuroblastoma — a cancer of the nervous system — accounts for 15 percent of childhood cancer deaths and has bleak survival probabilities of less than 40 percent. There is a strong familial association and it was predicted more than 30 years ago that there is a genetic element to the disease.

The genetic discovery stems from a global research collaboration headed by Children’s Hospital of Philadelphia. The study involved screening the genomes of 20 affected families (a total of 176 people), looking for single letter changes in the DNA code, which are mutations known as single nucleotide polymorphisms, or SNPs.

STSI was sought to participate in the study based on its expertise in conducting structural studies of SNPs identified in genes and proteins. Researchers at STSI looked at the mutations identified through the genetic screening and determined precisely where on the protein structure those mutations resided, enabling them to predict whether the mutations are likely to have meaningful biological effects.

Researchers identified inherited mutations in the gene encoding ALK, a tyrosine kinase receptor, as being responsible for causing the disease in the majority of families. SNP mutations in this gene were also found in sporadic cases of neuroblastoma. The mutations mapped to a part of the ALK gene that cause it to be constantly active in promoting cell proliferation, explaining its ability to contribute to the cancer.

“This is a significant finding because it means we can screen for people who carry mutations to see if they are at risk for neuroblastoma,” said Nicholas Schork, Ph.D., director of biostatistics for STSI. “It also helps pave the way for finding drugs that may inhibit the deleterious actions of these mutations.”

Schork and STSI researcher and Dickinson scholar Ali Torkamani, Ph.D. are among the authors of the article in Nature online, titled “Identification of ALK as a major familial neuroblastoma predisposition gene.”

The research opens the door for a long-sought-after molecular diagnostic test for predisposition to neuroblastoma, as well as identifying ALK as a promising drug target.

About Scripps Translational Science Institute

Founded in 2006, Scripps Translational Science Institute (STSI) is an initiative of Scripps Health, in collaboration with The Scripps Research Institute. STSI initiates research designed to help move basic research from the lab to the patient bedside, bridging the gap between basic science and clinical trials.

STSI programs include , which focuses on defining the genes that underlie susceptibility to disease; and , which is geared toward testing individualized treatment and prevention strategies in collaboration with pharmaceutical, medical device, biotechnology and diagnostic companies

About Scripps Health

Founded in 1924 by philanthropist Ellen Browning Scripps, Scripps Health is a $2 billion nonprofit community health system based in San Diego, Calif. Scripps treats a half-million patients annually through the dedication of 2,600 affiliated physicians and 12,200 employees among its five acute-care hospital campuses, home health care services, and an ambulatory care network of clinics, physician offices and outpatient centers.

Recognized as a leader in the prevention, diagnosis, and treatment of disease, Scripps is also at the forefront of clinical research and graduate medical education. Read more about Scripps Health.

Contact: Steve Carpowich
Phone: 858-678-7183
E-mail: carpowich.stephen@scrippshealth.org