University of Southern California

University of Miami

The United States of America, as Represented by the Secretary, Department of Health and Human Services

University of Oregon

Usc/norris Comprehensive Cancer Ctr.

State of Oregon

Peter A Jones

Gangning Liang

Mark L Gonzalgo

Kimberly D Siegmund

Jonathan Cheng

Sheng-Fang Su

Peter W Laird

Sheldon B Greer

Victor E Marquez

Yoshitaka Tomigahara

Martin Widschwendter

Eric U Selker

Theresa K Kelly

Cindy B Matsen

Isabel D C Markl

Hualin Fu

A method for the prediction, prognosis and/or diagnosis of bladder cancer or bladder cancer recurrence in a subject, the method includes: providing a test sample from the subject; measuring DNA methylation levels of at least a portion of two or more polynucleotides selected from the group consisting of HOXA9, SOX1, NPY, IRAK3, L1-MET, and ZO2 in the test sample; calculating a risk score based on the measured DNA methylation levels, comparing the calculated risk score to a cut-off value derived from a reference DNA methylation profile based on DNA methylation levels of the one or more biomarkers derived from a control group, members of which had bladder cancer; and based on the comparison calculated risk score to the cut-off value, determining at least one of: (1) whether bladder cancer has recurred; (2) whether there is likelihood that the bladder cancer will recur; and (3) whether the patient has bladder cancer.

DNA methylation biomarkers for bladder cancer

A method for the prediction, prognosis and/or diagnosis of bladder cancer or bladder cancer recurrence in a subject, the method includes: providing a test sample from the subject; measuring DNA methylation levels of at least a portion of two or more polynucleotides selected from the group consisting of HOXA9, SOXI, NPY, IRAK3, L1-MET, and Z02 in the test sample; calculating a risk score based on the measured DNA methylation levels, comparing the calculated risk score to a cut-off value derived from a reference DNA methylation profile based on DNA methylation levels of the one or more biomarkers derived from a control group, members of which had bladder cancer; and based on the comparison calculated risk score to the cut-off value, determining at least one of: (1) whether bladder cancer has recurred; (2) whether there is likelihood that the bladder cancer will recur; and (3) whether the patient has bladder cancer.

Disclosed are methods and kits for genome-wide methylation of GpC sites and for genome-wide chromatin structural determination. Specifically, the methods and kits of the present invention make possible the simultaneous determination of endogenous DNA methylation state and chromatin architecture across the entire genome.

Methods and kits for genome-wide methylation of GpC sites and genome-wide determination of chromatin structure

Particular embodiments provide novel and clinically useful DNA methylation predictors of hormone receptor status, and predictors of response to endocrine (e.g., hormonal) and non-endocrine breast cancer therapy. The ESR1 gene, encoding the estrogen receptor (ER) alpha proved to be the preferred predictor of progesterone receptor (PR) status, while methylation of the PGR gene, encoding PR, was the preferred predictor of ER status. ESR1 methylation outperformed hormone receptor status as a predictor of clinical response in patients treated with antiestroges (e.g., tamoxifen), while promoter methylation of the CYP1B1 gene, encoding a tamoxifen and estradiol metabolizing cytochrome P450, predicted response differentially in tamoxifen-treated and non-treated patients. High levels of promoter methylation of the ARH1 gene, encoding a RAS-related small G-protein, were shown to be preferred predictors of better survival in patients who had not received tamoxifen therapy.

Association of the DNA methylation profile of the CYP1B1 gene with response to adjuvant therapy in breast cancer

Zebularine has hypomethylating activity, and can be used to inhibit, reverse, and/or reduce DNA methylation in vivo and in vitro. Methods are provided for treating methylation-linked conditions through the application of 2-pyrimidinone derivatives, such as Zebularine. Compositions, including pharmaceutical compositions, comprising such derivatives are also provided. Also provided are kits for use in inhibiting DNA methylation, which kits include an amount of a 2-pyrimidinone derivative.

Inhibitor of DNA methylation

There is disclosed a cancer diagnostic method based upon DNA methylation differences at specific CpG sites. Specifically, the inventive method provides for a bisulfite treatment of DNA, followed by methylation-sensitive single nucleotide primer extension (Ms-SNuPE), for determination of strand-specific methylation status at cytosine residues.

Cancer diagnostic method based upon DNA methylation differences

There is disclosed 103 novel methylation-altered DNA sequences ('marker sequences') that have distinct methylation patterns in cancer, compared to normal tissue. In many instances, these marker sequences represent novel sequences not found in the GenBank data base, and none of these marker sequences have previously been characterized with respect to their methylation pattern in human cancers including, but not limited to those of bladder and prostate. These 103 sequences have utility as diagnostic, prognostic and therapeutic markers in the treatment of human cancer, and as reagents in kits for detecting methylated CpG-containing nucleic acids.

Methylation altered DNA sequences as markers associated with human cancer

Growing community of inventors

La Canada, CA, United States of America

Peter A Jones