The Cancer Genome Atlas Reports Molecular Characterization of Brain Tumors

A large-scale, multi-dimensional analysis of the genomic characteristics of glioblastoma, the most common primary brain tumor in adults, provides new insights into the roles of several genes and defines core biological pathways altered in tumor development [1]. The new Cancer Genome Atlas study, published in the September 4th advanced online edition of the journal Nature, also reveals a link between the DNA repair enzyme MGMT and a hypermutation phenotype, and has potential implications for the diagnosis and treatment of glioblastoma.

Glioblastoma is the most common and aggressive type of brain cancer. Patients newly diagnosed with glioblastoma have a median survival of approximately one year with generally poor response to therapy [2]. Gene expression profiling studies suggest multiple subtypes of glioblastoma that, when fully defined, may allow for more personalized therapeutic approaches [3-4].

Novel Gene Suppresses Tumor Growth in Multiple Cancers

A novel gene was discovered recently that suppresses the growth of human tumors in a number of different cancers. The study, published in the journal Nature Medicine, found that the gene HACE1, an acronym for HECT domain and ankyrin repeat containing, E3 ubiquitin protein ligase 1, is able to help cells deal with various forms of stress that cause tumor formation [1].

Tumor Suppressors and Oncogenes

The cell cycle is a series of ordered events that occur in a cell between it’s initial formation and eventual duplication and division into two daughter cells. Cells in the human body normally reproduce up to ~50 times [1], doubling their number with each cell cycle. Stem cells provide a pool of dividing cells to replace those that have died.

Interphase, the period between cell divisions, is where most cells remain for at least 90% of the cell cycle. Interphase consists of three phases: G1 (for gap 1), S phase (for synthesis) and G2 (for gap 2). During G1, the cell undergoes rapid growth and metabolic activity, including production of RNA and synthesis of protein. For the cell to divide and produce an identical copy of itself, its genome must be duplicated. DNA replication occurs in S phase. During G2, cell growth continues and the cell prepares for division. Cell division or mitosis occurs in M phase.

In normal cells, during G1 there are specific genes that control the speed of the cell cycle. These genes, called tumor suppressors and oncogenes, are mutated (meaning damaged) in cancer cells and can result in uncontrolled reproduction. Additionally, unlike normal cells, cancer cells do not stop reproducing after ~50 divisions. Thus, a cancer is an uncontrolled proliferation of cells.