WO2002097119A2 - Verwendung des nachweises der expression von splice-varianten von gen21 für die diagnose und therapie von tumorerkrankungen - Google Patents
Verwendung des nachweises der expression von splice-varianten von gen21 für die diagnose und therapie von tumorerkrankungen Download PDFInfo
- Publication number
- WO2002097119A2 WO2002097119A2 PCT/DE2002/002001 DE0202001W WO02097119A2 WO 2002097119 A2 WO2002097119 A2 WO 2002097119A2 DE 0202001 W DE0202001 W DE 0202001W WO 02097119 A2 WO02097119 A2 WO 02097119A2
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- expression
- gen215
- gen217
- sequence
- splice variants
- Prior art date
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Classifications
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
- C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
- C12Q1/6886—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/118—Prognosis of disease development
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/158—Expression markers
Definitions
- the invention relates to the use of splice variants of the sequence Gen21 for the diagnosis and therapy of tumor diseases. Areas of application are medicine and the pharmaceutical industry.
- chromosome 3p21.3 which may contain tumor suppressor genes, was discovered by somatic genetic mapping of tumor cell lines, tumor biopsies and pre-malignant lesions from human lung and breast tissue samples (1). Twenty-five genes were found in this region, which encompasses approximately 630 kilobases. Four of these genes showed reduced mRNA expression in non-small cell lung cancer. Mutations were found in 6 of these genes, including Gen21, which led to the formation of an altered amino acid sequence. However, none of these mutations occurred in more than 10% of the lung carcinomas tested, and nothing is known about the prognostic significance of these genes.
- the postulated tumor suppressor gene has not yet been detected, and that in particular the sequence Gen21 has not been identified as a tumor suppressor gene.
- the sequence Gen21 has not been identified as a tumor suppressor gene.
- no data on the occurrence or function of Gen21 in colorectal or other carcinomas have been published.
- the object of the invention was to find new tumor suppressor genes on chromosome 3p21.3 which are suitable for the diagnosis and therapy of tumor diseases.
- Gene215 is a spliced variant of Gen217 that lacks two sequence sections. The mRNA sequence of Gen215 is therefore shorter than that of Gen217. However, this does not apply to the protein sequence. Since the RNA sequence of Gen217 contains a stop codon, the encoded peptide sequence of Gen217 is shortened compared to that of Gen215.
- the gene sequences of Gen215 and Gen217 are shown in Figures 2 and 3.
- Gen215 was not expressed in about 40% of the cases.
- Gen215 is therefore a substance which can be used for prognostic, diagnostic and therapeutic purposes in the case of tumor diseases.
- the expression of Gen215 represents a prognostic factor for the diagnosis of tumor diseases.
- the invention therefore relates to the use of Gen215 for the prognosis, the concentration of the Gen215 protein and / or the expression of its genes encoding it being determined, e.g. by determining the mRNA expression using RT-PCR or expression determination using microarrays by immobilizing a corresponding oligonucleotide sequence.
- Gen215 By measuring the expression of Gen215 in tumor tissue from resected specimens or biopsies from patients, prognoses for the survival (life expectancy e.g. after operations or chemotherapy treatments) of a patient can be made. If Gen215 is expressed normally, about 80% of the patients are still alive after 60 months. If Gen215 is not expressed, only 40% of the patients are still alive after 60 months (unpublished).
- the invention further relates to therapeutic agents for the treatment of tumor diseases which contain substances which activate the expression of genes which encode Gen215 or Gen217. These therapeutic substances are applied to the respective tumor cells.
- the therapeutic agents are preferably in formulations for parenteral administration or for gene therapy use.
- Genchip from Affymetrix or other microarrays measured.
- the RT-PCR is carried out as follows. Carcinoma tissue is in liquid nitrogen
- RNA is extracted using the GITC
- Beta actin is co-amplified in the same reaction vessel.
- Beta-actin is amplified with the following primers and detected with the probe.
- Probe TET-CCA TCG TCC ACC GCA AAT GCT TC-TAMRA
- the length of the reaction product is 80 base pairs.
- the Gen215 is amplified with the following primers and detected with the probe
- Qgen215 IV probe FAM-ATCCTGTGCGGGTGACTCGGGA-2 & 4
- the length of the reaction product is 156 base pairs.
- Figure 1 shows the survival of patients with or without expression of Gen215 in the tissue.
- the survival curve was obtained according to Kaplan-Meier and the significance of the differences was calculated using the log-rank test.
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Analytical Chemistry (AREA)
- Zoology (AREA)
- Pathology (AREA)
- General Health & Medical Sciences (AREA)
- Immunology (AREA)
- Genetics & Genomics (AREA)
- Wood Science & Technology (AREA)
- Engineering & Computer Science (AREA)
- General Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biotechnology (AREA)
- Hospice & Palliative Care (AREA)
- Biophysics (AREA)
- Physics & Mathematics (AREA)
- Biochemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Molecular Biology (AREA)
- Oncology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Microbiology (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Abstract
Description
Claims
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AU2002317169A AU2002317169A1 (en) | 2001-05-31 | 2002-05-30 | Use of the indication of the expression of splice variants of gene 21 for the diagnosis and treatment of tumour diseases |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE10126472.0 | 2001-05-31 | ||
DE2001126472 DE10126472A1 (de) | 2001-05-31 | 2001-05-31 | Verwendung des Nachweises der Expression von Splice-Varianten von Gen21 für die Diagnose und Therapie von Tumorerkrankungen |
Publications (2)
Publication Number | Publication Date |
---|---|
WO2002097119A2 true WO2002097119A2 (de) | 2002-12-05 |
WO2002097119A3 WO2002097119A3 (de) | 2003-05-30 |
Family
ID=7686732
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/DE2002/002001 WO2002097119A2 (de) | 2001-05-31 | 2002-05-30 | Verwendung des nachweises der expression von splice-varianten von gen21 für die diagnose und therapie von tumorerkrankungen |
Country Status (3)
Country | Link |
---|---|
AU (1) | AU2002317169A1 (de) |
DE (1) | DE10126472A1 (de) |
WO (1) | WO2002097119A2 (de) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2004044152A2 (en) * | 2002-11-12 | 2004-05-27 | Wyeth | A novel pth responsive gene |
-
2001
- 2001-05-31 DE DE2001126472 patent/DE10126472A1/de not_active Withdrawn
-
2002
- 2002-05-30 WO PCT/DE2002/002001 patent/WO2002097119A2/de not_active Application Discontinuation
- 2002-05-30 AU AU2002317169A patent/AU2002317169A1/en not_active Abandoned
Non-Patent Citations (6)
Title |
---|
DATABASE BIOSIS [Online] BIOSCIENCES INFORMATION SERVICE, PHILADELPHIA, PA, US; 1991 ZEEH A ET AL: "THE PRODUCT OF THE SPLIT SUNY GENE OF BACTERIOPHAGE T4 IS A PROCESSED PROTEIN" Database accession no. PREV199293027928 XP002231566 & JOURNAL OF BACTERIOLOGY, Bd. 173, Nr. 21, 1991, Seiten 6980-6985, ISSN: 0021-9193 * |
DATABASE EBI [Online] Database accession no. AAX39651 XP002231569 * |
DATABASE EBI [Online] Database accession no. AF040707 XP002231568 * |
DATABASE EBI [Online] Database accession no. BC002791.1 XP002231567 * |
LERMAN MICHAEL I ET AL: "The 630-kb lung cancer homozygous deletion region on human chromosome 3p21.3: Identification and evaluation of the resident candidate tumor suppressor genes." CANCER RESEARCH, Bd. 60, Nr. 21, 1. November 2000 (2000-11-01), Seiten 6116-6133, XP002231565 ISSN: 0008-5472 in der Anmeldung erw{hnt * |
STOSS ET AL: GENE THER MOL BIOL, [Online] Bd. 5, Dezember 2000 (2000-12), Seiten 9-30, XP002231564 Gefunden im Internet: <URL:stamms-lab.net/pdfs/stossGT.pdf> [gefunden am 2003-02-18] * |
Also Published As
Publication number | Publication date |
---|---|
WO2002097119A3 (de) | 2003-05-30 |
DE10126472A1 (de) | 2002-12-05 |
AU2002317169A1 (en) | 2002-12-09 |
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