Altered genes play role in development of brain tumors

The interaction between a network of altered genes appears to play an important role in the development and progression of brain tumors, revealed by researchers in the Journal of the American Medical Association — JAMA.

Malignant gliomas (brain tumors) are associated with disproportionately high illness and death and are among the most devastating of tumors. Particular genomic alterations are fundamental to both their formation and their malignant progression.

“Chromosomal alterations presumably exert their tumor-promoting effect on glioma cells by modifying the expression or function of distinct genes, which map to those alterations, so as to deregulate growth factor signaling and survival pathways. For many chromosomal alterations, the biologically relevant target genes remain to be discovered,” the authors write.

Oncogenic research on brain tumors has focused on the tumor-promoting or tumor-suppressive function of target genes within individual chromosomal alterations. However, these alterations do not exist in isolation, nor do single genes account for gliomagenesis. Rather, there may be mechanistic links to genes at other, coincident alterations, according to background information in the article.

Markus Bredel, M.D., Ph.D., of the Northwestern Brain Tumor Institute at Northwestern University Feinberg School of Medicine, Chicago, and colleagues examined the relationships of tumor-promoting genes in gliomas. The study included genomic profiles and clinical profiles of 501 patients with gliomas (45 tumors in an initial discovery set collected between 2001 and 2004 and 456 tumors in validation sets made public between 2006 and 2008) from multiple academic centers in the United States and The Cancer Genome Atlas Pilot Project (TCGA).

The researchers found: “The alteration of multiple networking genes by recurrent chromosomal aberrations in gliomas deregulates critical signaling pathways through multiple, cooperative mechanisms. These mutations, which are likely due to nonrandom selection of a distinct genetic landscape [a consistent pattern of chromosomal alterations] during gliomagenesis, are associated with patient prognosis.”

The authors add that the identification of such gene alterations in gliomas prompts evaluation of their potential as therapeutic targets.

Source: Journal of the American Medical Association, USA



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