certain FUBP1, crucial role in emergence of certain forms of a low grade brain tumor, oligodendroglioom, evidenced by genes studies. Article posted 9 August 2011

9 August 2011: source: Science DOI: 1210557 10.1126/science.

Scientists have discovered that mutations (changes) at two certain genes, CIC and FUBP1, seem to play a crucial role in the emergence of a low grade brain tumours in a specific area of the brain, so-called oligodrendroglioom. What this means for the possible treatment of this form of brain tumors describes Meds cape in an article about this study. Here is a quote from this article:

"The study illustrates an important pathway that can be further studied for its therapeutic potential," noted coauthor Kenneth Kinzler, PhD, professor and codirector of the Ludwig Center at Johns Hopkins, when speaking with Meds cape Medical News.

Another member of the research team explained how a therapy might work with these mutations.

The genes identified are tumor suppressor genes, says coauthor Hai Yan, MD, PhD, associate professor of pathology at Duke. "Tumor suppressor genes like the ones we found, FUBP1, CIC and won't be targeted directly by small molecules, because the mutated gene products result in loss of function, but the pathways that these genes are involved in could be targeted," Dr. Yan explained.

The researchers initially anaplastic oligodendrogliomas analyzed 7, which are a higher-grade form of the disease. In total, they sequenced the coding exons or 20,687 genes.

They identified nonsynonymous somatic mutations, affecting 200 225 genes in the 7 tumors. There were an average of 32.1 nonsynonymous somatic mutations per tumor. This is similar to the number found in glioblastomas (35.6), the most common type of adult brain tumor.

There were a number of notable mutations identified, the authors say. On the strength of the findings in the initial 7 tumors, the investigators analyzed 27 more tumors for a select group of mutations, including those of CIC and FUBP1. Overall, 23 mutations or CIC or were identified in the 34 FUBP1 oligodendroglioma samples analyzed.

"Our identification or inactivating mutations or CIC or a substantial fraction of FUBP1 in oligodendrogliomas is likely to provide important insights into the pathogenesis of these tumors, as well as help refine their diagnosis, prognosis, and treatment options," they write.

CIC and FUBP1 genes are known to regulate cell-signaling processes, and CIC mutations have been linked — although sarcoma and breast and prostate cancers rarely — to, note the authors. Read more >>>>>

Here is the abstract of the study: genes

Mutations in CIC and contribute to human FUBP1 oligodendroglioma

  1. Chetan Bettegowda1,2,*,
  2. Nishant Agrawal1,3,*,
  3. Yuchen Jiao1 ,
  4. Mark Sauces1,
  5. Laura D. Wood4 ,
  6. Ralph H.
Hruban,4
  • Fausto J. Rodriguez4,
  • Daniel P. Cahill5,
  • Roger McLendon6 ,
  • Gregory Riggins1,2 ,
  • Victor E. Velculescu1,
  • Sueli Mieko Oba Shinjo-7 ,
  • Suely Kazue Nagahashi
    • Marie7,
  • Bert Vogelstein1,†,
  • Darell Bigner6,
  • Hai Yan6,†,
  • Nickolas Papadopoulos1,†,
  • Kenneth W. Kinzler1,
    • href = "http://www.sciencemag.org/content/early/2011/08/03/science.1210557.abstract?sid=fe96f17d-ac89-4c28-8935-c80ada70f377#corresp-1" >†

    + Author Affiliations

    1. 1Ludwig Center for Cancer Genetics and Howard Hughes Medical Institutions, Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21287, USA.
    2. 2Department of Neurosurgery, The Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA.
    3. 3Department of Otolaryngology-Head and Neck Surgery, The Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA.
    4. 4Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA.
    5. 5Department of Neurosurgery, The University of Texas MD Anderson Cancer Center and Baylor College of Medicine, Houston, TX 77030, USA.
    6. 6The Preston Robert Tisch Brain Tumor Center at Duke, The Pediatric Brain Tumor Foundation Institute and the Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA.
    7. 7Department of Neurology, School of Medicine, University of Sao Paulo, Sao Paulo, Brazil.
    1. †To whom correspondence should be addressed. Email: vogelbe@jhmi.edu (e.g.); yan00002@mc.duke.edu (H.Y.); npapado1@jhmi.edu (p); kinzlke@jhmi.edu (K.W.K.) ↵* These authors contributed equally to this work.

      Abstract:

    Oligodendrogliomas are the second most common malignant brain tumor in adults and chromosomes 1 p and 19q exhibit characteristic losses or. To identify the molecular genetic basis for this alteration, we performed exomic sequencing or seven tumors. Among other changes, we found that the CIC gene (homolog of the Drosophila gene capicua) on chromosome 19q somatically mutated in six cases and that the was FUBP1 gene [encoding far upstream element (FUSE) binding protein] on chromosome 1 p somatically mutated in two tumors was. Examination of 27 additional oligodendrogliomas revealed 12 and 3 more tumors with mutations or CIC and FUBP1, respectively, 58% of which were predicted to result in truncations or theencoded proteins. These results suggest a critical role for these genes in the biology and pathology of oligodendrocytes