Methods of detecting insulator dysfunction and oncogene activation for screening, diagnosis and treatment of patients in need thereof
Номер патента: EP3390656A1
Опубликовано: 24-10-2018
Автор(ы): Bradley Bernstein, Daniel TARJAN, William Flavahan, Yotam DRIER
Принадлежит: General Hospital Corp
Опубликовано: 24-10-2018
Автор(ы): Bradley Bernstein, Daniel TARJAN, William Flavahan, Yotam DRIER
Принадлежит: General Hospital Corp
Реферат: The present application generally to the diagnosis and treatment of diseases resulting from the alteration of chromatin boundaries between topologically-associated domains. In particular, the present application relates to detection of mutations causing DNA hvpermethylation phenotypes, CpG methylation within CTCF binding motifs, and aberrant gene expression caused by altered chromatin topology. Applicants show that IDH mutant gliomas exhibit hyper-methyiation at CTCF binding sites, compromising binding of this methylation- sensitive insulator protein. Applicants also demonstrate that loss of CTCF at a domain boundary permits a constitutive enhancer to aberrantly interact with the receptor tyrosine kinase gene PDGFRA, a prominent glioma oncogene. Thus, Applicants have uncovered that IDH mutations may promote gliomagenesis by disrupting chromosomal topology and allowing aberrant regulatory interactions that induce oncogene expression.
Methods of detecting insulator dysfunction and oncogene activation for screening, diagnosis and treatment of patients in need thereof
Номер патента: US20200224274A1. Автор: Bradley Bernstein,Daniel TARJAN,Yotam DRIER,William Flavahan. Владелец: General Hospital Corp. Дата публикации: 2020-07-16.