Oligodendroglioma drive genes

US9873917B2 · kind B2 · utility

Assignees

• THE JOHNS HOPKINS UNIVERSITY · US
• Duke University · US

Inventors

• Bert Vogelstein · Baltimore, US
• Kenneth W. Kinzler · Baltimore, US
• Chetan Bettegowda · Charlotte, US
• Nishant Agrawal · Baltimore, US
• Nickolas Papadopoulos · Towson, US
• Darell Bigner · Mebane, US
• Hai Yan · Chapel Hill, US
• Roger McLendon · Durham, US

Key dates

• Filing date: Jul 18, 2012
• Grant date: Jan 23, 2018
• Expiry date: Jan 6, 2034

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C12Q2600/158
• WIPO field: Biotechnology
• WIPO sector: Chemistry

Abstract

Oligodendrogliomas are the second most common malignant brain tumor in adults. These tumors often contain a chromosomal abnormality involving a pericentromeric fusion of chromosomes 1 and 19, resulting in losses of the entire short arm of the former and the long arm of the latter. To identify the molecular genetic basis for this alteration, we performed exomic sequencing of seven anaplastic oligodendrogliomas with chromosome 1p and 19q losses. Among other changes, we found that that CIC (homolog of the Drosophila gene capicua) on chromosome 19q was somatically mutated in six of the seven cases and that FUBP1 (far upstream element (FUSE) binding protein) on chromosome 1p was somatically mutated in two of the seven cases. 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.