High-Resolution Genome-Wide Mapping of Genetic Alterations in Human Glial Brain Tumors

TLDR

High‑resolution genome‑wide mapping of chromosomal alteration boundaries aims to localize genes driving gliomagenesis and define genetic subgroups of glial brain tumors. The study used cDNA microarray‑based comparative genomic hybridization across 42,000 clones to profile copy‑number alterations in 54 gliomas of diverse histology and grade. The approach precisely sized critical amplicons and deletions, uncovered numerous new genetic aberrations, revealed recurrent chromosomal patterns that cluster gliomas into distinct genetic subgroups, linked specific alterations to astrocytic or oligodendrocytic phenotypes, and identified five novel minimally deleted regions harboring candidate tumor‑suppressor genes such as TOPORS, FANCG, RAD51, TP53BP1, and BIK.

Abstract

Abstract High-resolution genome-wide mapping of exact boundaries of chromosomal alterations should facilitate the localization and identification of genes involved in gliomagenesis and may characterize genetic subgroups of glial brain tumors. We have done such mapping using cDNA microarray-based comparative genomic hybridization technology to profile copy number alterations across 42,000 mapped human cDNA clones, in a series of 54 gliomas of varying histogenesis and tumor grade. This gene-by-gene approach permitted the precise sizing of critical amplicons and deletions and the detection of multiple new genetic aberrations. It has also revealed recurrent patterns of occurrence of distinct chromosomal aberrations as well as their interrelationships and showed that gliomas can be clustered into distinct genetic subgroups. A subset of detected alterations was shown predominantly associated with either astrocytic or oligodendrocytic tumor phenotype. Finally, five novel minimally deleted regions were identified in a subset of tumors, containing putative candidate tumor suppressor genes (TOPORS, FANCG, RAD51, TP53BP1, and BIK) that could have a role in gliomagenesis.