Duke University

Johns Hopkins University

Zachary James Reitman

Hai Yan

Bert Vogelstein

Kenneth W Kinzler

Nickolas Papadopoulos

Darell D Bigner

Chetan Bettegowda

Yuchen Jiao

Patrick J Killela

John Howard Sampson

Bryan Daehahn Choi

We surveyed 1,230 tumors of 60 different types and found that tumors could be divided into types with low (&#x3c;15%) and high (&#x2265;15%) frequencies of TERT promoter mutations. The nine TERT-high tumor types almost always originated in tissues with relatively low rates of self renewal, including melanomas, liposarcomas, hepatocellular carcinomas, urothelial carcinomas, squamous cell carcinomas of the tongue, medulloblastomas, and subtypes of gliomas (including 83% of primary glioblastoma, the most common brain tumor type). TERT and ATRX mutations were mutually exclusive, suggesting that these two genetic mechanisms confer equivalent selective growth advantages. In addition to their implications for understanding the relationship between telomeres and tumorigenesis, TERT mutations provide a biomarker for the early detection of urinary tract and liver tumors and aid in the classification and prognostication of brain tumors.

promoter mutations in gliomas and a subset of tumors

Tert promoter mutations in gliomas and a subset of tumors

Described herein are compositions and methods for generating oxidoreductases for enantioselective reactions. Described herein are compositions and methods for generating neomorphic (R)-2-hydroxyacid dehydrogenases capable of enzymatically converting a 1-carboxy-2-ketoacid to a 1-carboxy-(R)-2-hydroxyacid, or the reverse reaction. Illustrative examples include (a) (R)-2-hydroxyadipate dehydrogenase and uses thereof for converting 2-oxoadipate to (R)-2-hydroxyadipate, or the reverse reaction; and (b) (R)-2-hydroxyglutarate dehydrogenase and uses thereof for converting 2-oxoglutarate to (R)-2-hydroxyglutarate, or the reverse reaction. Also described herein are compositions and methods for generating non-natural microbial organisms to enzymatically convert 2-oxoadipate to (E)-2-hexenedioate or adipate, or to enzymatically convert 2-oxoglutarate to (E)-2-pentenedioate or glutarate, or the respective reverse reactions.

Oxidoreductases for enantioselective reactions

Growing community of inventors

Durham, NC, United States of America

Zachary James Reitman