New regulatory circuit identified for aggressive, malignant brain tumor

Apr 07, 2008

Research using a newly developed algorithm has significantly advanced understanding of the molecular events associated with the most common primary brain tumor in adults, human glioblastoma (GBM). The research, published by Cell Press in the April issue of the journal Cancer Cell, validates known genetic aberrations and identifies events not previously linked with GBM, thereby elucidating new directions for potential therapeutic strategies.

GBM is a devastating neurological cancer that is characterized by widespread invasion, robust angiogenesis and a stubborn resistance to conventional and targeted treatments. Previous research has implicated a long and highly complex list of genes in GBM pathogenesis, emphasizing the need for a systemic prioritization that would separate relevant target genes from bystanders and provide detailed knowledge of the complex interactions between multiple disrupted genes and downstream targets.

Dr. Lynda Chin from Dana-Farber Cancer Institute, Dr. Cameron Brennan from Memorial Sloan-Kettering Cancer Center and their colleagues used a high-resolution genome topography scan (GTS) algorithm to both define and rank the patterns of genomic alterations associated with GBM in primary samples and cell lines. Using this new methodology, the researchers discovered an unanticipated co-deletion pattern among closely related INK genes in the GBM oncogenome.

Specifically, the researchers identified a frequent co-deletion of p18INK4C and p16INK4A, a pattern unique to glioblastoma. Functional reconstitution of p18INK4C in GBM cells lacking both p16INK4A and p18INK4C resulted in impaired cell cycle progression and tumorigenic progression. Depletion of p18INK4C in p16INK4A-deficient primary glial cells or established GBM cells enhanced tumorigenicity while acute suppression of p16INK4A in primary glial cells induced an increase in p18INK4C. “These results uncover an unanticipated tumor suppressor role for p18INK4C in human GBM wherein it functions cooperatively with other INK4 family members to constrain inappropriate glial cell proliferation,” concludes Dr. Chin.

“This study also demonstrates that GTS can address one critical need in the development of a functional map of GBM genetic targets: namely, to prioritize those genomic alterations that are likely to be of importance from among those that are more likely to be bystanders of the cancer process,” offers Dr.Brennan. “Downstream functional validation of high probability candidates should yield novel GBM genes and potential targets for therapeutic intervention.”

Source: Cell Press

Explore further: Experts set strategic priorities for lymphoma research

add to favorites email to friend print save as pdf

Related Stories

Recommended for you

Experts set strategic priorities for lymphoma research

15 hours ago

A committee of lymphoma experts today unveiled a strategic roadmap identifying key priority areas in both infrastructure and research that will be critical for advancing treatments for people with lymphoma. The report is meant to inform future research directions as well as fund ...

Research aims to reduce health care disparities

15 hours ago

The lesbian, gay, bisexual, transgender/transsexual, queer/questioning and intersex (LGBTQI) population has been largely understudied by the medical community. Researchers at Moffitt Cancer Center found that the LGBTQI community ...

Promising drug target identified in medulloblastoma

16 hours ago

Scientists at Dana-Farber/Boston Children's Cancer and Blood Disorders Center have identified a protein critical to both the normal development of the brain and, in many cases, the development of medulloblastoma, a fast-growing ...

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.