Epigenomics Ag

Other

Dietrich, Dimo

Theo De Vos

Joe Lograsso

Fabian Model

Volker Liebenberg

Cathy Lofton-Day

Jennifer Maas

Andrew Sledziewski

Matthias Ballhause

Kurt Berlin

Matthias Schuster

Dimo Dietrich

Reimo Tetzner

Catherine E Lofton-Day

Antje Kluth Lukas

Ralf Lesche

Andrew Z Sledziewski

Shannon Payne

Ute Wagner

Reinhold Wasserkort

Heike Ziebarth

Manfred Schmitt

Juergen Distler

Nadia Harbeck

Oliver Hartmann

Sabine Maier

Manuel Krispin

Susan Cottrell

Peter Adorjan

Thomas Koenig

Jürgen Distler

Heinz Hoefler

John W Martens

John Foekens

Theo Devos

Almuth Marx

Tamas Rujan

Antje Kluth

Inko Nimmrich

Anne Fassbender

Volkmar Mueller

Philipp Schatz

Ina Schwope

Joern Dietrich

Volkmar c/o Department Of Gynecology Müller

John Martens

Michael Wandell

Reinhold Wassenkort

Jörn Dietrich

Catherine Lofton-Day

Heinz Höfler

Thomas König

The invention relates to, among others, a method for assessing a prognosis of a patient with a malignant disease and/or for predicting the response of a patient with a malignant disease to immunotherapy. For this purpose, a DNA methylation analysis is carried out on at least one immunoregulatory gene of cells of the malignant disease and/or T lymphocytes which interact with the cells of the malignant disease, said gene coding for an immune checkpoint selected from B7 proteins and the receptors thereof, MHC-peptide complex-binding co-receptors, the members of the tumor necrosis factor receptor superfamily TNFRSF9, CD40, TNFRSF4, TNFRSF18, and CD27, the members of the immunoglobulin superfamily TIGIT, BTLA, HAVCR2, BTNL2 and CD48, and the andenosine-binding adenosine 2A receptor.

Method for assessing a prognosis and predicting a response of patients with malignant diseases to immunotherapy

A method for determining a mutation in genomic DNA is described. The method is characterized in that the mutation analysis is performed with genomic DNA, in which at least a part of the cytosines contained therein has previously been converted into uracil or another base with a base pairing behavior or molecular weight distinguishable from that of cytosine.

Method for determining a mutation in genomic DNA, use of the method and kit for carrying out said method

The invention relates to methods for predicting the response of a patient with a malignant disease to immunotherapy with a pharmaceutical compound that is designed to inhibit an immunoregulatory effect of an immune checkpoint selected from cytotoxic T-lymphocyte-associated protein 4 (CTLA4) and its ligands Cluster of differentiation 80 (CD80) and Cluster of Differentiation 86 (CD86). The methods are based on a DNA methylation analysis of the CTLA4 gene of cells of the malignant disease and/or T lymphocytes interacting with said cells of the malignant disease.

Method for predicting response of patients with malignant diseases to immunotherapy

Aspects of the present invention relate to compositions and methods for providing DNA fragments from a remote sample. In particular aspects a remote sample comprising DNA is provided, DNA is isolated from the remote sample, and the isolated DNA is treated in a way which allows differentiation of methylated and unmethylated cytosine. Additional, particular embodiments provide compositions and methods for methylation analysis of DNA derived from a remote sample. Other aspects provide for compositions and methods of whole genome amplification of bisulfite treated DNA. Other aspects provide methods for determining the presence or absence of methylation of at least one cytosine, or a series of cytosines in cis, in human DNA of a blood sample, a plasma sample, a serum sample or a urine sample from a human individual.

Method for determining the presence or absence of methylation in a sample

Provided herein are methods, nucleic acids and kits for detecting a cell proliferative disorder. Also provided herein are genomic sequences of RASSF'-2, the methylation patterns of which have utility for the improved detection of cell proliferative disorders, thereby enabling the improved diagnosis and treatment of patients.

Methods and nucleic acids for analyses for cellular proliferative disorders

The invention provides methods, nucleic acids and kits for determining the prognosis of a subject having cell proliferative disorder, preferably cancer. The invention discloses genomic sequences the methylation patterns of which have utility for the improved detection of said disorder, thereby enabling the improved diagnosis and treatment of patients.

Methods and nucleic acids for analyses of cell proliferative disorders

The invention provides methods, nucleic acids and kits for detecting prostate cell proliferative disorders. The invention discloses genomic sequences the methylation patterns of which have utility for the improved detection of said disorder, thereby enabling the improved diagnosis and treatment of patients.

Methods and nucleic acids for the analysis of gene expression associated with the development of prostate cell proliferative disorders

The present invention relates to modified and genomic sequences, to oligonucleotides and/or PNA-oligomers for detecting the cytosine methylation state of genomic DNA, as well as to a method for predicting the disease free survival and/or response of a subject with a cell proliferative disorder of the breast tissues, to endocrine treatment.

Methods for the prognosis of breast cancer

Aspects of the present invention relate to compositions and methods for providing DNA fragments from an archived sample (e.g., paraffin-embedded and/or fixed-tissue biopsies, etc.). Particular aspects provide methods whereby high yields of DNA are isolated as well as a substantial portion of the DNA consists of long DNA fragments, and where the isolated genomic DNA is free of associated or cross-linked contaminants like proteins, peptides, amino acids or RNA. The methods are facile, cost-effective, and are characterized by high reproducibility and reliability. Particular aspects provide methods for providing DNA fragments derived from an archived sample, wherein the yield of DNA before, for example, an amplification step is at least 20%, and amplicons up to a length of about 1,000 base pairs are amplifiable.

Method for providing DNA fragments derived from an archived sample

Particular aspects provide methods for specific amplification of template DNA in the presence of potentially contaminating PCR products from previous amplification experiments. Particular embodiments comprise, in a first step, contacting DNA with a bisulfite solution, which sulfonates unmethylated (but not methylated) cytosines, resulting in cytosine deamination and generation of sulfonated uracil. Such sulfonation protects the template nucleic acid from being a target for the enzyme uracil-DNA-glycosylase (UNG), whereas any contaminating DNA, which contains unprotected unsulfonated or desulfonated uracils, is degraded enzymatically while the UNG is active. After UNG treatment and inactivation thereof, the sulfonated uracil bases are converted into uracil by desulfonation. Such aspects have substantial utility for decontamination of nucleic acid samples; e.g., for avoiding amplification of 'carry over products' in the context of DNA methylation analysis. In further aspects, the inventive methods can be generally used as simplified methods of bisulfite treatment.

Method for the carry-over protection in DNA amplification systems targeting methylation analysis achieved by a modified pre-treatment of nucleic acids

Aspects of the present invention relate to compositions and methods for providing DNA fragments from an archived sample (e.g., paraffin-embedded and/or fixed-tissue biopsies, etc). Particular aspects provide methods whereby high yields of DNA are isolated as well as a substantial portion of the DNA consists of long DNA fragments, and where the isolated genomic DNA is free of associated or cross-linked contaminants like proteins, peptides, amino acids or RNA. The methods are facile, cost-effective, and are characterized by high reproducibility and reliability. Particular aspects provide methods for providing DNA fragments derived from an archived sample, wherein the yield of DNA before, for example, an amplification step is at least 20%, and amplicons up to a length of about 1,000 base pairs are amplifiable.

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Berlin, Germany

Dimo Dietrich