Method of diagnosing bladder cancer

a bladder cancer and cancer technology, applied in the field of bladder cancer diagnosis, can solve the problems of affecting the treatment effect, and affecting the treatment effect, and achieve the effect of improving the treatment effect, and improving the treatment

Inactive Publication Date: 2012-04-26
ERASMUS UNIV MEDICAL CENT ROTTERDAM ERASMUS MC
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  • Summary
  • Abstract
  • Description
  • Claims
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AI Technical Summary

Benefits of technology

[0064]Restriction-enzyme based methods are based on the inability of methylation sensitive restriction enzymes to cleave methylated cytosines in their recognition site. The identification of the methylation status relies on Southern hybridization techniques or PCR and is based on the length of the digested DNA fragment. The inability to digest methylated sequences results in longer fragments, indicating a methylated CpG dinucleotide. Restriction-enzyme based methods are simple, rapid and highly sensitive and are suitable for genome-wide methylation analyses as well as marker discovery techniques.

Problems solved by technology

Cystoscopy is an uncomfortable, invasive, and expensive procedure, but currently remains the gold standard for detection of recurrences.
Because patients have to be monitored perpetually and have a long-term survival, bladder cancer is the most expensive cancer when calculated on a per patient basis.
Unfortunately, this method is limited by its sensitivity, which is especially poor for low-grade tumors.

Method used

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  • Method of diagnosing bladder cancer
  • Method of diagnosing bladder cancer
  • Method of diagnosing bladder cancer

Examples

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example 1

[0086]The CpG island hypermethylations as indicated in the Tables 1-5 are the result of comparative studies using well characterized patient samples. Both tumor samples and controls were analyzed. The DNA was extracted directly from the tumor and control tissue. DNA samples were analyzed using a CpG island microarray comprising 200.000 CpG islands (Agilent Technologies Inc.). The results obtained are indicated in the various Tables 1-5 as listed herein.

example 2

Materials & Methods

[0087]Patient samples, ethics statement and DNA isolation Samples from 44 fresh frozen bladder cancer tissues were collected, representing 29 non-muscle invasive tumors (19 with FGFR3 mutation (NMI-mt) and 10 without (NMI-wt)) and 15 muscle-invasive tumors (MI). Tumor tissue of patients was obtained from the Department of Urology of the Erasmus MC, Rotterdam. The medical-ethical committee of the Erasmus MC Rotterdam approved the project. All patients gave written informed consent. For validation, 90 formalin-fixed, paraffin-embedded (FFPE) bladder cancer samples (27 Ta NMI-mt, 13 Ta NMI-wt, 10 T1-mt, 14 T1-wt, 26 MI) were collected from the Department of Pathology. Usage of these samples was performed according to standards presented in “The Code for Proper Secondary Use of Human Tissues in The Netherlands” (http: / / www.federa.org). Tumor samples were included only if at least 80% of the sample consisted of cancer cells, as verified by H&E staining. DNA from tumor ...

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Abstract

The present invention relates to a method of diagnosing cancer in a subject comprising detecting in the DNA of said subject at least one hypermethylated CpG island associated with said cancer, wherein an elevation in the level of methylation in said CpG island of said subject, relative to the level of methylation in said CpG island of a control subject, is indicative of said CpG island being hypermethylated.

Description

FIELD OF THE INVENTION[0001]The present invention is in the field of bladder cancer diagnosis, and in particular the methods for predicting the progression of bladder cancer tumors. The invention provides diagnostic methods and diagnostic compositions for use in such methods. The invention further provides therapeutic targets for treating specific forms of bladder cancers.BACKGROUND OF THE INVENTION[0002]Bladder cancer is the fifth most common cancer in the western world with an incidence of 20 new cases per year per 100,000 people in the U.S. Unfortunately, these statistics do not include superficial pTa bladder cancer, which represents the most common type of bladder cancer. In the Netherlands, the incidence of both superficial and invasive bladder cancer is estimated as about 30 new cases per year per 100,000 people. This is in accordance with data from global cancer statistics for the western world. Superficial bladder tumors are removed by transurethral resection. However, up t...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): C12Q1/68C07H21/04C40B20/00A61K38/02
CPCC12Q1/6886C12Q2600/16C12Q2600/154C12Q2600/118
Inventor ZWARTHOFF, ELLEN CATHARINAVAN TILBORG, ANNECHIENA GEERTRUIDE
Owner ERASMUS UNIV MEDICAL CENT ROTTERDAM ERASMUS MC
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