GENETIC ALTERATIONS IN ISOCITRATE DEHYDROGENASE AND OTHER GENES IN MALIGNANT GLIOMA

• Main Authors: Victor VELCULESCU, Giovanni PARMIGIANI, Rachel KARCHIN, Sian JONES, Kenneth W. KINZLER, D. Williams PARSONS, Xiaosong ZHANG, Rebecca J. LEARY, Gregory RIGGINS, Nickolas PAPADOPOULOS, Bert VOGELSTEIN, Philipp ANGENENDT, Hai YAN, Jimmy Cheng-Ho LIN, Darell BIGNER, Chien-Tsun KUAN
• Format: Patent
• Language: English; Spanish
• Published: 03.10.2018
• Subjects: BEER; BIOCHEMISTRY; CHEMISTRY; COMPOSITIONS OR TEST PAPERS THEREFOR; COMPOSITIONS THEREOF; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL ORENZYMOLOGICAL PROCESSES; CULTURE MEDIA; ENZYMOLOGY; HUMAN NECESSITIES; HYGIENE; MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEICACIDS OR MICROORGANISMS; MEDICAL OR VETERINARY SCIENCE; METALLURGY; MICROBIOLOGY; MICROORGANISMS OR ENZYMES; MUTATION OR GENETIC ENGINEERING; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; PROCESSES OF PREPARING SUCH COMPOSITIONS; PROPAGATING, PRESERVING OR MAINTAINING MICROORGANISMS; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS; SPIRITS; VINEGAR; WINE

We found mutations of the R132 residue of isocitrate dehydrogenase 1 (IDH1) in the majority of grade II and III astrocytomas and oligodendrogliomas as well as in glioblastomas that develop from these lower grade lesions. Those tumors without mutations in IDH1 often had mutations at the analogous R172 residue of the closely related IDH2 gene. These findings have important implications for the pathogenesis and diagnosis of malignant gliomas. La presente invención se refiere a un polipéptido mutante para usarse en el tratamiento de un tumor de GBM, en donde el polipéptido mutante comprende al menos 8 residuos contiguos de aminoácido de: una proteína de IDH1 humana en un tumor humano, los al menos 8 residuos contiguos de aminoácido que comprenden el residuo 132, en donde el residuo 132 no es arginina; o una proteína de IDH2 humana encontrada en un tumor humano, los a l menos 8 residuos contiguos de aminoácido que comprenden el residuo 172, en donde el residuo 172 no es arginina .