Mutations in CIC and FUBP1 Contribute to Human Oligodendroglioma

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

Virginia

D. K. Ludwig Fund for Cancer Research

Pediatric Brain Tumor Foundation

Duke Comprehensive Cancer Center Core

Burroughs Wellcome Fund

James S. McDonnell Foundation

Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)[04/12433-6]

Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)[01/12898-4]

National Cancer Institute Division of Cancer Prevention (NCI/NIH)[N01-CN-43302]

National Institutes of Health (NIH)[CA43460]

National Institutes of Health (NIH)[CA57345]

National Institutes of Health (NIH)[CA11898]

National Institutes of Health (NIH)[CA121113]

National Institutes of Health (NIH)[CA62924]

National Institutes of Health (NIH)[RC2DE020957]

National Institutes of Health (NIH)[NS20023]

NIH/NCI Institutional National Research Service[T32 CA009574]