skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Predictive and therapeutic markers in ovarian cancer

Abstract

Cancer markers may be developed to detect diseases characterized by increased expression of apoptosis-suppressing genes, such as aggressive cancers. Genes in the human chromosomal regions, 8q24, 11q13, 20q11-q13, were found to be amplified indicating in vivo drug resistance in diseases such as ovarian cancer. Diagnosis and assessment of amplification levels certain genes shown to be amplified, including PVT1, can be useful in prediction of poor outcome of patient's response and drug resistance in ovarian cancer patients with low survival rates. Certain genes were found to be high priority therapeutic targets by the identification of recurrent aberrations involving genome sequence, copy number and/or gene expression are associated with reduced survival duration in certain diseases and cancers, specifically ovarian cancer. Therapeutics to inhibit amplification and inhibitors of one of these genes, PVT1, target drug resistance in ovarian cancer patients with low survival rates is described.

Inventors:
; ; ; ;
Publication Date:
Research Org.:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1082960
Patent Number(s):
8,404,829
Application Number:
11/814,798
Assignee:
The Regents of the University of California (Oakland, CA) ; The Board of Regents, University of Texas System (Austin, TX) LBNL
DOE Contract Number:
AC02-05CH11231
Resource Type:
Patent
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES

Citation Formats

Gray, Joe W., Guan, Yinghui, Kuo, Wen-Lin, Fridlyand, Jane, and Mills, Gordon B.. Predictive and therapeutic markers in ovarian cancer. United States: N. p., 2013. Web.
Gray, Joe W., Guan, Yinghui, Kuo, Wen-Lin, Fridlyand, Jane, & Mills, Gordon B.. Predictive and therapeutic markers in ovarian cancer. United States.
Gray, Joe W., Guan, Yinghui, Kuo, Wen-Lin, Fridlyand, Jane, and Mills, Gordon B.. Tue . "Predictive and therapeutic markers in ovarian cancer". United States. doi:. https://www.osti.gov/servlets/purl/1082960.
@article{osti_1082960,
title = {Predictive and therapeutic markers in ovarian cancer},
author = {Gray, Joe W. and Guan, Yinghui and Kuo, Wen-Lin and Fridlyand, Jane and Mills, Gordon B.},
abstractNote = {Cancer markers may be developed to detect diseases characterized by increased expression of apoptosis-suppressing genes, such as aggressive cancers. Genes in the human chromosomal regions, 8q24, 11q13, 20q11-q13, were found to be amplified indicating in vivo drug resistance in diseases such as ovarian cancer. Diagnosis and assessment of amplification levels certain genes shown to be amplified, including PVT1, can be useful in prediction of poor outcome of patient's response and drug resistance in ovarian cancer patients with low survival rates. Certain genes were found to be high priority therapeutic targets by the identification of recurrent aberrations involving genome sequence, copy number and/or gene expression are associated with reduced survival duration in certain diseases and cancers, specifically ovarian cancer. Therapeutics to inhibit amplification and inhibitors of one of these genes, PVT1, target drug resistance in ovarian cancer patients with low survival rates is described.},
doi = {},
journal = {},
number = ,
volume = ,
place = {United States},
year = {Tue Mar 26 00:00:00 EDT 2013},
month = {Tue Mar 26 00:00:00 EDT 2013}
}

Patent:

Save / Share:
  • Seven families, selected for breast cancer segregation, have been analyzed for chromosome 17q12-q23 linkage to breast and ovarian cancer. In two of them, linkage is seen with most markers tested, increasing toward the most proximal region, but without informative recombinations above NM23. In the remaining families, no linkage is observed. Families with 17q linkage are not easily distinguished by clinical characteristics such as early onset (mean age at diagnosis [le]45 years) or organs involved. In fact, the family with the highest lod scores ([ge]2.3) belongs to the [open quotes]later onset[close quotes] (>45 years) category of families. Interestingly, prostatic cancer ismore » the most frequent malignancy, after breast cancer, in the families that were studied (13 cases total, all metastasizing) and is especially prevalent in males presumed to carry the trait. Of 16 paternal carriers, 7 (44%) had developed prostatic cancer. Haplotype analysis in families with 17q linkage reveals two further prostatic cases as potential carriers. The authors propose that breast cancer genes may predispose to prostatic cancer in male carriers. 12 refs., 2 figs., 2 tabs.« less
  • Immunocytology of ascitic fluid of a patient with ovarian cancer demonstrated reactivity with two tumor-associated monoclonal antibodies, AUA1 and HMFG2. AUA1 radiolabeled with 48.6 mCi /sup 131/I was given intraperitoneally. There was a reduction in the rate of reaccumulation of ascites. Cytology of recurrent ascites revealed reactivity with antibody HMFG2 but not AUA1. The patient was further treated intraperitoneally with 39.0 mCi /sup 131/I-labeled HMFG2. There has been no reaccumulation of ascites. It is concluded that antibody-guided irradiation may be an effective treatment of malignant ascites secondary to ovarian cancer. Furthermore, this case illustrates the specificity of antibody interactions inmore » the mediation of therapeutic effect and the possibility of tumor selection after irradiation with a single monoclonal antibody. If specificity plays a role, all major specificities should be covered by an appropriate panel of radioactively labeled antibodies. It is recommended that for comprehensive therapy of malignant ascites secondary to ovarian cancer, a mixture of antibodies such as HMFG2 and AUA1 should be used.« less
  • The authors have conducted linkage analysis in 16 breast cancer families, 13 of which are classified as site-specific breast cancer families and 3 of which are classified as breast-ovary families. Linkage analysis has largely focused on a single extended breast-ovary family. Analysis of all families combined shows significant evidence for linkage to 17q (LOD = 3.63 at [theta] = .0, for linkage to NME1), confirming the observations of Hall et al. and Narod et al. Many families were consistent with linkage, but their limited size and informativeness precluded confirmation of linkage. A putative recombinant in a breast-ovary family suggests thatmore » BRCA1 is distal to D17S250. 12 refs., 3 figs.« less
  • Genes on chromosomes 17q and 18q have been shown to code for putative tumor suppressors. By a combination of allele-loss studies on sporadic ovarian carcinomas and linkage analysis on a breast/ovarian cancer family, the authors have investigated the involvement of such genes in these diseases. Allele loss occurred in sporadic tumors from both chromosome 17p, in 18/26 (69%) cases, and chromosome 17q, in 15/22 (68%) cases. In the three familial tumors studied, allele loss also occurred on chromosome 17 (in 2/3 cases for 17p markers and in 2/2 cases for a 17q allele). Allele loss on chromosome 18q, at themore » DCC (deleted in colorectal carcinomas) locus, was not as common (6/16 cases [38%]) in sporadic ovarian tumors but had occurred in all three familial tumors. The results of linkage analysis on the breast/ovarian cancer family suggested linkage between the disease locus and 17q markers, with a maximum lod score of 1.507 obtained with Mfd188 (D17S579) polymorphism at 5% recombination. The maximum lod score for DCC was 0.323 at 0.1% recombination. In this family the results are consistent with a predisposing gene for breast/ovarian cancer being located at chromosome 17q21. 24 refs., 1 fig., 3 tabs.« less