Mutations signaling poor neuroblastoma prognosis identified

Dec 4 2012

By Helen Albert, Senior medwireNews Reporter

Children with neuroblastoma who have mutations in the ARID1A and ARID1B genes in their tumors have a poor prognosis compared with those without these alterations, show study findings.

"These cancers have a wide spectrum of clinical outcomes, with some that are highly curable and others very lethal," commented study author Victor Velculescu (Johns Hopkins University, Baltimore, Maryland, USA) in a press statement.

"Part of the reason for this variety in prognosis may be due to changes in the ARID1A and ARID1B genes."

As described in Nature Genetics, the researchers collected samples from the tumors of 71 children with neuroblastoma. They performed genetic analysis using a variety of techniques and found that each tumor had an average of 19 somatic mutations in coding genes.

Mutations in ARID1A and ARID1B, which have not previously been associated with neuroblastoma, were seen in eight (11%) of the tumors sampled.

These mutations were associated with a poor prognosis: all but one of the children with these mutations died of progressive disease.

Children with ARID1A gene alterations had a mean survival of 386 days compared with 1689 days for those without these mutations. In addition, for those with both ARID1A and ARID1B mutations, the survival time was 6.41 times shorter than for those without these mutations.

"Unfortunately, children with these mutations have a particularly aggressive, treatment-resistant form of neuroblastoma," co-author Michael Hogarty, also from Johns Hopkins University, told the press.

Velculescu and team also developed a technique to identify rearranged DNA and dysregulation of chromatin in the serum of four of the patients, which they hope will "provide new approaches for the management of patients with neuroblastoma."

Hogarty explained: "All tumors harbor genetic mistakes that leave a fingerprint in the DNA, and tumor DNA is often detected in the blood as well."

He added: "We may be able to develop a blood test, personalized to each cancer patient, to detect their tumor fingerprint in circulating blood DNA. This would permit oncologists to more accurately monitor patients for treatment response and recurrence, and offer a tool to help guide treatment decisions."

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