Dataset Information

Epigenetic Classifiers for Precision Diagnosis of Brain Tumors.

ABSTRACT: DNA methylation profiling has proven to be a powerful analytical tool, which can accurately identify the tissue of origin of a wide range of benign and malignant neoplasms. Using microarray-based profiling and supervised machine learning algorithms, we and other groups have recently unraveled DNA methylation signatures capable of aiding the histomolecular diagnosis of different tumor types. We have explored the methylomes of metastatic brain tumors from patients with lung cancer, breast cancer, and cutaneous melanoma and primary brain neoplasms to build epigenetic classifiers. Our brain metastasis methylation (BrainMETH) classifier has the ability to determine the type of brain tumor, the origin of the metastases, and the clinical-therapeutic subtype for patients with breast cancer brain metastases. To facilitate the translation of these epigenetic classifiers into clinical practice, we selected and validated the most informative genomic regions utilizing quantitative methylation-specific polymerase chain reaction (qMSP). We believe that the refinement, expansion, integration, and clinical validation of BrainMETH and other recently developed epigenetic classifiers will significantly contribute to the development of more comprehensive and accurate systems for the personalized management of patients with brain metastases.

SUBMITTER: Orozco JI

PROVIDER: S-EPMC6444760 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Epigenetic Classifiers for Precision Diagnosis of Brain Tumors.

Orozco Javier Ij JI Manughian-Peter Ayla O AO Salomon Matthew P MP Marzese Diego M DM

Epigenetics insights 20190331

DNA methylation profiling has proven to be a powerful analytical tool, which can accurately identify the tissue of origin of a wide range of benign and malignant neoplasms. Using microarray-based profiling and supervised machine learning algorithms, we and other groups have recently unraveled DNA methylation signatures capable of aiding the histomolecular diagnosis of different tumor types. We have explored the methylomes of metastatic brain tumors from patients with lung cancer, breast cancer, ...[more]

PMID: 30968063

Similar Datasets

Project description:BackgroundDespite advancements in the successful use of immunotherapy in treating a variety of solid tumors, applications in treating brain tumors have lagged considerably. This is due, at least in part, to the lack of well-characterized antigens expressed within brain tumors that can mediate tumor rejection; the low mutational burden of these tumors that limits the abundance of targetable neoantigens; and the immunologically "cold" tumor microenvironment that hampers the generation of sustained and productive immunologic responses. The field of mRNA-based therapeutics has experienced a boon following the universal approval of COVID-19 mRNA vaccines. mRNA-based immunotherapeutics have also garnered widespread interest for their potential to revolutionize cancer treatment. In this study, we developed a novel and scalable approach for the production of personalized mRNA-based therapeutics that target multiple tumor rejection antigens in a single therapy for the treatment of refractory brain tumors.MethodsTumor-specific neoantigens and aberrantly overexpressed tumor-associated antigens were identified for glioblastoma and medulloblastoma tumors using our cancer immunogenomics pipeline called Open Reading Frame Antigen Network (O.R.A.N). Personalized tumor antigen-specific mRNA vaccine was developed for each individual tumor model using selective gene capture and enrichment strategy. The immunogenicity and efficacy of the personalized mRNA vaccines was evaluated in combination with anti-PD-1 immune checkpoint blockade therapy or adoptive cellular therapy with ex vivo expanded tumor antigen-specific lymphocytes in highly aggressive murine GBM models.ResultsOur results demonstrate the effectiveness of the antigen-specific mRNA vaccines in eliciting robust anti-tumor immune responses in GBM hosts. Our findings substantiate an increase in tumor-infiltrating lymphocytes characterized by enhanced effector function, both intratumorally and systemically, after antigen-specific mRNA-directed immunotherapy, resulting in a favorable shift in the tumor microenvironment from immunologically cold to hot. Capacity to generate personalized mRNA vaccines targeting human GBM antigens was also demonstrated.ConclusionsWe have established a personalized and customizable mRNA-therapeutic approach that effectively targets a plurality of tumor antigens and demonstrated potent anti-tumor response in preclinical brain tumor models. This platform mRNA technology uniquely addresses the challenge of tumor heterogeneity and low antigen burden, two key deficiencies in targeting the classically immunotherapy-resistant CNS malignancies, and possibly other cold tumor types.

Dataset Information

Epigenetic Classifiers for Precision Diagnosis of Brain Tumors.

Publications

Epigenetic Classifiers for Precision Diagnosis of Brain Tumors.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets