Genetic Mutations Responsible For Childhood Brain Tumors

Posted: July 23, 2012 at 11:13 pm

July 23, 2012

redOrbit Staff & Wire Reports Your Universe Online

Researchers from several prominent medical institutions claim that they have identified several genetic mutations responsible for medulloblastoma, the most common malignant type of childhood brain tumor.

There are four recognized subtypes of medulloblastomas, which occur in the part of the brain responsible for controlling balance and other complex motor functions (the cerebellum), Boston Childrens Hospital researchers explained in a recent statement.

These tumors are treated through a combination of surgery, chemotherapy, and radiation, and while survival rate for this form of cancer is approximately 70%, hospital officials note that those who overcome the disease are usually not able to live independently due to side-effects related both to the tumor and the treatment methods.

Doctors have historically classified medulloblastoma patients as either standard or high risk based on biopsy results, but have long suspected that what we call medulloblastoma could actually be several different diseases, they said. Over the last two years, studies by researchers have bolstered this view by dividing medulloblastoma into four molecular subtypes based on gene expression profiles and copy number variations. Each subtype has a distinct survival rate, ranging from 20 to 90 percent.

Now, Dr. Scott Pomeroy, Neurologist-in-Chief at Boston Childrens Hospital and a neuro-oncologist at the Dana-Farber/Childrens Hospital Cancer Center (DF/CHCC), and colleagues used advanced sequencing techniques to study the medulloblastoma tumors of 92 patients. They then compared that information with DNA obtained from matched blood samples from those same subjects and discovered 12 single-letter errors in the genetic code (also known as point mutations) that occurred frequently in all types of the cancer.

Functionally, the mutated genes fell into two broad categories: genes like Shh and Wnt that play direct roles in molecular pathways controlling cell growth, and genes like DDX3X and GPS2 that play more of a coaching role, modulating the activity of other genes, the researchers said. Taken as a whole, the studys results confirm the view of medulloblastoma as a family of tumors driven by disruptions in just a few common mechanisms. However, the form those disruptions take the actual mutations or genomic changes can vary from tumor to tumor.

We tend to treat all medulloblastomas as one disease without taking into account how heterogeneous the tumors are at the molecular level, Yoon-Jae Cho, an assistant professor of neurology and neurological sciences at the Stanford University School of Medicine and senior author of a report published by the journal Nature, said in a statement. This paper represents a finer-grained view of the genetic landscape of these tumors and provides us with some leads on how to develop new therapies.

While no single tumor in the study carried all 12 mutations, the researchers said that they were able to categorize the tumors according to which mutations they possessed, discovering that certain tumors can be resistant to standard treatments because of their genetic signatures. Cho said that treatment of the disease could be enhanced, and post-treatment side effects reduced, if doctors characterized the genetic signatures of medulloblastoma patients first.

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Genetic Mutations Responsible For Childhood Brain Tumors

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