In a genome sequencing study of 74 neuroblastoma tumors in children, scientists at the Johns Hopkins Kimmel Cancer Center and the Children's Hospital of Philadelphia (CHOP) found that patients with changes in two genes, ARID1A and ARID1B, survive only a quarter as long as patients without the changes. The discovery could eventually lead to early identification of patients with aggressive neuroblastomas who may need additional treatments.
Neuroblastomas affect nerve tissue throughout the body and are the most common, non-blood cancer in children. "These cancers have a wide spectrum of clinical outcomes, with some that are highly curable and others very lethal," says Victor Velculescu, M.D., Ph.D., professor of oncology and co-director of the Cancer Biology Program at Johns Hopkins. "Part of the reason for this variety in prognosis may be due to changes in the ARID1A and ARID1B genes."
Velculescu said these powerful "bully" genes were not identified in other gene sequencing studies of neuroblastoma, most likely because the Johns Hopkins-CHOP researchers used sequencing and analytical methods that looked for larger, structural rearrangements of DNA in addition to changes in the sequence of individual chemical base-pairs that form DNA. A report of their work appears in the Dec. 2 issue of Nature Genetics.
Of the 74 tumors in the study, 71 were analyzed for both rearrangements and base-pair changes. Cancer-specific mutations were found in a variety of genes previously linked to neuroblastoma, including the ALK and MYCN genes. In eight of the 71 patients, the investigators found alterations in the ARID1A and ARID1B genes, which normally control the way DNA folds to allow or block protein production.
The children with ARID1A or ARID1B gene changes had far worse survival, on average, than those without the genetic alterations — 386 days compared with 1,689 days. All but one of these patients died of progressive disease, including one child whose neuroblastoma was thought to be highly curable.
The scientists were also able to detect and monitor neuroblastoma-specific genetic changes in the blood of four patients included in the study, and correlated these findings to disease progression.
"Finding cancer-specific alterations in the blood could help clinicians monitor patients for relapse and determine whether residual cancer cells remain in the body after surgery," says Mark Sausen, a Johns Hopkins graduate student and one of the lead scientists involved in the research.
The Johns Hopkins-CHOP team plans to conduct further studies in larger groups of patients to confirm the ARID1A-ARID1B correlation to prognosis.
Johns Hopkins Medicine: http://www.hopkinsmedicine.org
This press release was posted to serve as a topic for discussion. Please comment below. We try our best to only post press releases that are associated with peer reviewed scientific literature. Critical discussions of the research are appreciated. If you need help finding a link to the original article, please contact us on twitter or via e-mail.
Analysis of millions of audio files has led one US company to claim that their software can predict how a person’s voice will make a listener feel
Bird flu outbreak now spreading through Midwest poultry could head east with fall migration
A little MRI video seems to settle the decades-old debate about that loud pop of the joints: It's all about bubbles. But imagine an air bag inflating, not the bursting of a balloon.
People who took acetaminophen responded less strongly to happy or sad photos in a small study. It's one of several studies suggesting that there's an overlap with pain and other feelings.
Teachers can become frustrated when students don't seem to try hard when it comes to schoolwork. There's a surprising explanation of why some students might not be putting their best effort forward.
Stress from serious events in first 14 years of life may be risk factor and one trigger for disease, finds Swedish study of 10,000 families
Legislators advance bill to tighten immunisation laws in the face of protest from small band of activists who believe parents should be allowed to opt out
To understand the appeal of extremist ideologies we need to look beyond the usual explanations, says a professor of epidemiology
It's not for the faint hearted but it works in mice. When enough hair is plucked out, an immune signal sent to nearby hair follicles triggers extra hair to grow back
A strange mix of living well and taking risks adds one more puzzle to the narcissistic personality