New insight into the genetics of brain tumor formation

Mar 17, 2008

In a G&D paper published online ahead of its April 1 print publication date, Dr. William Kaelin (Dana Farber Cancer Institute) and colleagues identify a potential new neuronal tumor suppressor.

“It has been suspected for decades that the short arm of chromosome 1 harbored one or more tumor suppressor genes because this region is deleted in a variety of tumors, including many neural crest-derived tumors. Our work suggests that KIFB{beta} is one such gene,” explains Dr. Kaelin.

Neural crest-derived tumors include neuroblastomas and medulloblastomas, which are the most common malignant pediatric solid tumors, as well as paragangliomas (relatively rare tumors of the sympathetic nervous system) and melanomas, the deadliest form of skin cancer.

Under normal developmental conditions, neural crest cells respond to diminishing growth factor signaling by inducing apoptosis, via a pathway involving the enzyme EglN3. However, the acquisition of mutations that enable cells to avoid apoptosis under low growth factor conditions provide a growth advantage and an effective route to tumorigenesis.

In this issue, Dr. Kaelin and colleagues identify that the protein KIF1B{beta} mediates EglN3-induced neuronal apoptosis, and thus provides a protective effect against the development of neural crest-derived tumors.

Importantly, KIF1B{beta} is positioned on the region of chromosome 1p that is deleted in a number of neural crest-derived tumors. The Kaelin group demonstrated that the supplementation of 1p-deleted neuroblastoma cancer cells with KIF1B{beta} protein is sufficient to restore apoptosis and identified inactivating point mutations in neural crest-derived tumors. They also showed that partial reduction of KIF1B{beta} - but not complete loss - confers protection against apoptosis, perhaps explaining why most 1p deleted tumors still retain the other KIF1B{beta} allele in its normal form.

While further research is needed to delineate the mechanism by which KIF1B{beta} induces apoptosis, this work opens up several avenues for investigation. For example, EglN3 is an oxygen-dependent enzyme that responds to a variety of signals and can be modulated with drug-like molecules. Dr. Kaelin points out that “an intriguing possibility is that an increase in EglN3 activity is responsible for the spontaneous regressions frequently observed in neonates who present with Neuroblastoma (so-called Stage 4S Neuroblastoma). Perhaps, in time, we can mimic this with EglN3 agonists.”

Source: Cold Spring Harbor Laboratory

Explore further: New gene technique identifies previously hidden causes of brain malformation

add to favorites email to friend print save as pdf

Related Stories

Water crisis threatens thirsty Sao Paulo

40 minutes ago

Sao Paulo is thirsty. A severe drought is hitting Brazil's largest city and thriving economic capital with no end in sight, threatening the municipal water supply to millions of people.

Canada to push Arctic claim in Europe

1 hour ago

Canada's top diplomat will discuss the Arctic with his Scandinavian counterparts in Denmark and Norway next week, it was announced Thursday, a trip that will raise suspicions in Russia.

Google to help boost Greece's tourism industry

1 hour ago

Internet giant Google will offer management courses to 3,000 tourism businesses on the island of Crete as part of an initiative to promote the sector in Greece, industry union Sete said on Thursday.

NKorea launch pad expansion 'nearing completion'

1 hour ago

A U.S. research institute says construction to upgrade North Korea's main rocket launch pad should be completed by fall, allowing Pyongyang (pyuhng-yahng) to conduct a launch by year's end if it decides to do so.

Recommended for you

Gene therapy protects mice from heart condition

Aug 20, 2014

A new gene therapy developed by researchers at the University of Missouri School of Medicine has been shown to protect mice from a life-threatening heart condition caused by muscular dystrophy.

Study finds crucial step in DNA repair

Aug 18, 2014

Scientists at Washington State University have identified a crucial step in DNA repair that could lead to targeted gene therapy for hereditary diseases such as "children of the moon" and a common form of ...

User comments : 0