National Cancer Institute®
Last Modified: August 1, 2002
UI - 10639883
AU - Reynolds PP; Benkendorf JL
TI - Genes and generalists: why we need professionals with added competencies.
SO - West J Med 1999 Nov-Dec;171(5-6):375-9
AD - Department of Medicine and History, Johns Hopkins University School of Medicine, Baltimore, MD, USA. email@example.com
UI - 12112655
AU - Yazici H; Glendon G; Yazici H; Burnie SJ; Saip P; Buyru F; Bengisu E;
TI - Andrulis IL; Dalay N; Ozcelik H BRCA1 and BRCA2 mutations in Turkish familial and non-familial ovarian cancer patients: a high incidence of mutations in non-familial cases.
SO - Hum Mutat 2002 Jul;20(1):28-34
AD - Centre for Cancer Genetics, Samuel Lunenfeld Research Institute, and Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Canada.
Ovarian cancer is a clinically important cancer in Turkey. The contribution of BRCA1 and BRCA2 to ovarian cancer in Turkish patients has not previously been described. In this study we investigated the presence of BRCA1 and BRCA2 mutations in 102 consecutively ascertained, hospital-based, ovarian cancer cases. Four out of 15 (26.7%, 95% confidence interval (CI), 7.8%-55.1%) familial cases were found to carry mutations in BRCA1. Thirteen of the 87 (14.9%, 95% CI, 7.5%-22.4%) non-familial cases had BRCA1 and BRCA2 mutations, six in BRCA1, and seven in BRCA2. We have further studied the non-familial ovarian cancer cases to determine which subgroups have a likelihood of carrying clinically important mutations. Our study shows that those Turkish ovarian cancer patients with serous histopathology harbor a high proportion of mutations (12/58, 20.7%, 95% CI, 10.3%-31.1%) compared to all non-familial cases (14.9%) regardless of pathology. Within the serous sub-group, those that were also diagnosed below age 50 have an even greater percentage of mutations (8/28, 28.6%, 95% CI, 11.8%-45.3%). Our findings demonstrate that a substantial proportion of Turkish ovarian cancer patients, both with and without a family history, carry BRCA1 and BRCA2 mutations, demonstrating the importance of BRCA1 and BRCA2 in the development of ovarian cancer in this population. Copyright 2002 Wiley-Liss, Inc.
UI - 12115565
AU - Obermair A; Schmid BC; Packer LM; Leodolter S; Birner P; Ward BG;
TI - Crandon AJ; McGuckin MA; Zeillinger R Expression of MUC1 splice variants in benign and malignant ovarian tumours.
SO - Int J Cancer 2002 Jul 10;100(2):166-71
AD - Queensland Centre for Gynaecological Cancer, Royal Brisbane Hospital, Brisbane, Australia. firstname.lastname@example.org
MUC1 is expressed on the surface of ovarian cancer cells. Nine different splice variants of MUC1 have been described, but no study has reported on the expression of MUC1 isoforms in human ovarian cancer. Our study compares patterns of expression of MUC1 splice variants of malignant and benign ovarian tumours. Ovarian tissue samples were taken from patients with benign ovarian tumours (n = 34) and from patients who had surgery for primary (n = 47) or recurrent (n = 8) ovarian cancer. RT-PCR for MUC1 splice variants A, B, C, D, X, Y, Z, REP and SEC was performed and their expression compared to clinical and histopathologic parameters. Variants A, D, X, Y and Z were more frequently expressed in malignant than in benign tumours. All primary ovarian cancer cases were positive for variant REP but negative for variant SEC. No significant association of the expression of MUC1 splice variants with the response to chemotherapy or patient survival could be demonstrated. Expression of MUC1 splice variants A, D, X, Y, Z and REP is associated with the presence of malignancy, whereas expression of MUC1/SEC is associated with the absence of malignancy. Copyright 2002 Wiley-Liss, Inc.
UI - 11843247
AU - Campos B; Diez O; Domenech M; Baena M; Pericay C; Balmana J; del Rio E;
TI - Sanz J; Alonso C; Baiget M BRCA2 mutation analysis of 87 Spanish breast/ovarian cancer families.
SO - Ann Oncol 2001 Dec;12(12):1699-703
AD - Servei de Genetica, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
BACKGROUND: It is estimated that about 5% -10% of breast cancer (BC) cases is due to inherited predisposition. Early works reported that 45%-50% of site-specific BC families had BRCA1 mutations and 25%-35% BRCA2 mutations. However, these percentages could have been overestimated and likely vary among the populations studied. PATIENTS AND METHODS: We analysed the BRCA2 gene in 87 Spanish breast/ovarian cancer families in which the BRCA1 mutation screening was negative. RESULTS: We detected 15 (17.2%) disease-causing mutations and 11 polymorphisms and unclassified variants. Four mutations were recurrent, and five were novel. Seven (47%) mutations were found in site-specific female BC families, five (33%) in families with OC cases, and three (20%) mutations in families with male BC cases. There was incomplete penetrance of the mutations in some families, and considerable phenotypic variations with respect to the age of diagnosis and cancer types. CONCLUSIONS: The percentage of mutations detected reinforces the possibility that some of these families have mutations in genes other than BRCA1 or BRCA2 that confer lower BC risks.
UI - 11948120
AU - Oberst MD; Johnson MD; Dickson RB; Lin CY; Singh B; Stewart M; Williams
TI - A; al-Nafussi A; Smyth JF; Gabra H; Sellar GC Expression of the serine protease matriptase and its inhibitor HAI-1 in epithelial ovarian cancer: correlation with clinical outcome and tumor clinicopathological parameters.
SO - Clin Cancer Res 2002 Apr;8(4):1101-7
AD - Department of Oncology, Lombardi Cancer Center, Georgetown University Medical Center, Washington, DC 20007, USA.
PURPOSE: Matriptase is a type II transmembrane serine protease expressed by cells of surface epithelial origin, including epithelial ovarian tumor cells. Matriptase cleaves and activates proteins implicated in the progression of ovarian cancer and represents a potential prognostic and therapeutic target. The aim of this study was to examine the expression of matriptase, and its inhibitor, hepatocyte growth factor activator inhibitor-1 (HAI-1), in epithelial ovarian cancer and to assign clinicopathological correlations. EXPERIMENTAL DESIGN: We have determined by immunohistochemistry the expression of matriptase and HAI-1 in 54 epithelial ovarian cancers. Statistical analyses of immunohistochemistry expression data with clinical outcome and clinicopathological parameters were then performed. RESULTS: Of 54 tumors tested, 39 (72%) and 11 (20%) were positive for matriptase and for HAI-1, respectively. All HAI-1-positive tumors were also matriptase positive. Analysis of clinicopathological parameters demonstrated a loss of matriptase associated with stage III/IV tumors as compared with stage I/II tumors (P = 0.030). There was also a loss of HAI-1 expression associated with stage III/IV tumors (P = 0.039). Of 34 stage I/II tumors, 28 (82%) stained positive for matriptase, and 10 (29%) stained positive for HAI-1; 10 (29%) tumors showed coexpression. Of 20 stage III/IV tumors, however, 11 stained positive for matriptase (55%), only 1 of which coexpressed HAI-1 (P = 0.039). CONCLUSIONS: Advanced-stage ovarian tumors that express matriptase are more likely to do so in the absence of its inhibitor, HAI-1, indicating that an imbalance in the matriptase:HAI-1 ratio could be important in the development of advanced disease. Such an imbalance could promote the proteolytic activity of matriptase and, consequently, a more invasive phenotype.
UI - 11948121
AU - Milliken D; Scotton C; Raju S; Balkwill F; Wilson J
TI - Analysis of chemokines and chemokine receptor expression in ovarian cancer ascites.
SO - Clin Cancer Res 2002 Apr;8(4):1108-14
AD - Cancer Research UK Translational Oncology Laboratory, St. Bartholomew's and the London, Queen Mary's School of Medicine and Dentistry, John Vane Science Centre London, United Kingdom.
PURPOSE: Ascitic disease is a common occurrence in human ovarian cancer, but it is unclear how the cellular composition of ascitic fluid is determined. Because chemokines can determine host cell infiltration in solid ovarian cancer, we assessed CC chemokine protein and CC chemokine receptor expression in ovarian cancer ascites. EXPERIMENTAL DESIGN: We used reverse transcription-PCR and RNase protection assay to determine CC chemokine and chemokine receptor mRNA expression and ELISA to measure CC chemokine protein levels. Flow cytometry was used to identify cell populations and their chemokine receptor protein expression. RESULTS: mRNA for the CC chemokines CCL2, -3, -4, -5, -8, and -22 was expressed in cell isolates from ascites samples, and the corresponding proteins were detected in ascitic fluid. mRNA for CC chemokine receptors CCR1, -2a, -2b, -3, -4, -5, and -8 was detected in cells from ascites. Fluorescence-activated cell-sorting analysis showed variable numbers of macrophages and CD3(+) T lymphocytes (predominantly CD4(+)) within ovarian cancer ascites. CD14(+) macrophages within ascites consistently expressed protein for CCR1, -2, and -5. CCR1 was expressed by >60% of all T cells, but more CD4(+) than CD8(+) T cells expressed CCR2 and -5. A direct correlation was found between the CCL5 concentration and CD3(+) T-cell infiltration. CONCLUSIONS: We conclude that there is a complex chemokine/chemokine receptor network in ovarian cancer ascites. However, associations between chemokine receptor expression, chemokine levels, and cell counts were limited.
UI - 12086881
AU - Foulkes WD
TI - Of mice and women.
SO - Cancer Cell 2002 Feb;1(1):11-2
AD - Program in Cancer Genetics, Department of Oncology, McGill University, Montreal, QC, Canada H3G 1A4. email@example.com
Transgenic mouse model faithfully reproduces human ovarian carcinoma and offers new opportunities for understanding the natural history of this frequently fatal disease.
UI - 12086888
AU - Orsulic S; Li Y; Soslow RA; Vitale-Cross LA; Gutkind JS; Varmus HE
TI - Induction of ovarian cancer by defined multiple genetic changes in a mouse model system.
SO - Cancer Cell 2002 Feb;1(1):53-62
AD - Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA. firstname.lastname@example.org
We have developed a mouse model for ovarian carcinoma by using an avian retroviral gene delivery technique for the introduction of multiple genes into somatic ovarian cells of adult mice. Ovarian cells from transgenic mice engineered to express the gene encoding the avian receptor TVA were efficiently infected in vitro with multiple vectors carrying coding sequences for oncogenes and marker genes. When target cells were derived from TVA transgenic mice deficient for p53, the addition of any two of the oncogenes c-myc, K-ras, and Akt were sufficient to induce ovarian tumor formation when infected cells were injected at subcutaneous, intraperitoneal, or ovarian sites. We demonstrated that the ovarian surface epithelium is the precursor tissue for these ovarian carcinomas, and that introduction of oncogenes causes phenotypic changes in the ovarian surface epithelial cells. The induced ovarian tumors in mice resembled human ovarian carcinomas in their rapid progression and intraperitoneal metastatic spread.
UI - 12053177
AU - Anand N; Murthy S; Amann G; Wernick M; Porter LA; Cukier IH; Collins C;
TI - Gray JW; Diebold J; Demetrick DJ; Lee JM Protein elongation factor EEF1A2 is a putative oncogene in ovarian cancer.
SO - Nat Genet 2002 Jul;31(3):301-5
AD - Hamilton Regional Cancer Centre, Room 450, 699 Concession Street, Hamilton, Ontario, L8V 5C2, Canada.
We have found that EEF1A2, the gene encoding protein elongation factor EEF1A2 (also known as eEF-1 alpha 2), is amplified in 25% of primary ovarian tumors and is highly expressed in approximately 30% of ovarian tumors and established cell lines. We have also demonstrated that EEF1A2 has oncogenic properties: it enhances focus formation, allows anchorage-independent growth and decreases the doubling time of rodent fibroblasts. In addition, EEF1A2 expression made NIH3T3 fibroblasts tumorigenic and increased the growth rate of ES-2 ovarian carcinoma cells xenografted in nude mice. Thus, EEF1A2 and the process of protein elongation are likely to be critical in the development of ovarian cancer.
UI - 12112530
AU - Denison SR; Becker NA; Ferber MJ; Phillips LA; Kalli KR; Lee J; Lillie
TI - J; Smith DI; Shridhar V Transcriptional profiling reveals that several common fragile-site genes are downregulated in ovarian cancer.
SO - Genes Chromosomes Cancer 2002 Aug;34(4):406-15
AD - Division of Experimental Pathology, Department of Laboratory Medicine and Pathology, Mayo Foundation, 200 First Street SW, Rochester, MN 55905, USA.
Previous transcriptional profiling analysis of 14 primary ovarian tumors identified approximately 12,000 genes as decreased in expression by at least twofold in one or more of the tumors sampled. Among those genes were several known to be mapped to common fragile sites (CFSs), some of which had previously been shown to exhibit a loss of expression in ovarian carcinoma. Therefore, we selected a subset of genes to determine whether they localized within CFSs. Of the 262 genes that were downregulated at least twofold in 13 of 14 tumors, 10 genes were selected based on the following criteria: localization to a CFS band; documented aberrations in at least one malignancy; and feasibility of scoring breakage at the specific CFS. Fluorescence in situ hybridization analysis was performed using bacterial artificial chromosome clones encompassing portions of the genes to determine the position of the genes relative to their corresponding CFSs. Nine genes were determined to localize within seven previously uncloned CFSs. Semiquantitative reverse-transcription/polymerase chain reaction analysis of the cell lines and primary ovarian tumors validated the downregulation of seven of the 10 genes. We identified portions of seven uncloned CFSs and provide data to suggest that several of the genes mapping within CFSs may be inactivated in ovarian cancer. Copyright 2002 Wiley-Liss, Inc.
UI - 12124354
AU - Chan KY; Ozcelik H; Cheung AN; Ngan HY; Khoo US
TI - Epigenetic factors controlling the BRCA1 and BRCA2 genes in sporadic ovarian cancer.
SO - Cancer Res 2002 Jul 15;62(14):4151-6
AD - Department of Pathology, Queen Mary Hospital and the University of Hong Kong, Hong Kong.
Hypermethylation of the BRCA1 promoter has previously been shown to cause reduced mRNA expression in both breast and ovarian cancers. Nothing is yet known of the expression pattern or methylation status of the promoter region of BRCA2 in sporadic ovarian cancer. Whereas our analysis of 30 sporadic ovarian carcinomas showed a statistically significant reduction of BRCA1 mRNA expression (P = 0.001), it also showed, in contrast, overexpression of BRCA2 mRNA (P = 0.002) in tumor compared with nontumor. Hypermethylation of the BRCA1 promoter highly correlated with decreased BRCA1 expression (P = 0.017). Methylated CpGs at the BRCA2 promoter were either absent or at very low levels in tumor DNA, whereas they were present at high levels in nontumor DNA. Such hypomethylation also correlated with elevated levels of BRCA2 mRNA (P = 0.043) and showed a statistically significant correlation with tumor stage (P = 0.037). This supports the role of methylation in BRCA2 contributing to the pathogenesis of sporadic ovarian cancer. Furthermore, 14 (58.2%) and 9 (56.3%) of all of the cases with aberrant BRCA mRNA expression and methylation patterns, respectively, demonstrated opposing mRNA expression and methylation patterns of the BRCA1 and BRCA2 genes within the same cases. Our findings suggest that both genes may be involved in the development of sporadic ovarian cancer.
UI - 11465542
AU - Pieretti M; Khattar NH; Smith SA
TI - Common polymorphisms and somatic mutations in human base excision repair genes in ovarian and endometrial cancers.
SO - Mutat Res 2001 Jan;432(3-4):53-9
AD - Department of Pathology, University of Kentucky, Lexington 40536, USA. email@example.com
The purpose of this study was to determine whether the human APEX and OGG1 genes, encoding proteins important in base excision repair (BER) of DNA, contain nucleotide sequence polymorphisms or are mutated somatically in tumors from women diagnosed with ovarian or endometrial cancer. Based upon the analysis of germline DNA from 83 individuals, 63 with ovarian cancer and 20 with endometrial cancer, we found two missense polymorphisms in APEX (Q51H and D 148E) and two missense (A3P and S326C) and one intronic (Exon 5-15 bp) polymorphism in OGG1. The frequencies of the various alleles (in the ovarian and endometrial cancer patients combined) were 4.8% for 51-His and 56.2% for 148-Glu in APEX, and 1.0% for 3-Pro and 20.0% for 326-Cys in OGG1. Somatic mutations in APEX (P112L, W188X and R237C) were identified in three of 20 endometrial tumors, but no mutations were identified in APEX in 43 ovarian tumors, or in OGG1 at either tumor site. Given the crucial role of the APEX and OGG1 proteins in BER of oxidative DNA damage, the identified polymorphisms are good candidates for genetic epidemiologic studies of cancer susceptibility, while the finding that three of 20 (15%) endometrial tumors have somatic mutations in APEX suggests that inactivation of the BER pathway is important for the development of endometrial cancer in at least a subset of cases.
UI - 12124814
AU - de la Hoya M; Sulleiro S; Osorio A; Diez O; Baiget M; Benitez J;
TI - Diaz-Rubio E; Caldes T Clustering of cancer-related mutations in a subset of BRCA1 alleles: a study in the Spanish population.
SO - Int J Cancer 2002 Aug 10;100(5):618-9
AD - Laboratory of Molecular Oncology, Hospital Universitario San Carlos, Madrid, Spain.
We have observed that the frequency of D17S855 short alleles (139 bp and 141 bp) in individuals carrying BRCA1 germline mutations is higher than in controls (54% vs. 31%, p = 0.0004). By unambiguously establishing mutation/D17S855 phase in 18 BRCA1-positive families, we find that most (11 of 15 different mutations) BRCA1 defects are linked to chromosomes with short alleles (OR = 8.21, 95% CI 1.97-39.32, p = 0.0007). We suggest that BRCA1 mutations are not randomly distributed but clustered in a subset of BRCA1 alleles that can be identified by D17S855 genotyping. Further analysis involving a larger set of mutations and different populations are needed to clarify the relevance of this unexpected finding. Copyright 2002 Wiley-Liss, Inc.
UI - 12040228
AU - Middelton L; Dimond E; Calzone K; Davis J; Jenkins J
TI - The role of the nurse in cancer genetics.
SO - Cancer Nurs 2002 Jun;25(3):196-206
AD - Urology Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Md. 20892-1873, USA.
Knowledge gained from the Human Genome Project and related genetic research is already impacting clinical oncology nursing practice. Because cancer is now understood to be a genetic disease, changes in the traditional approaches to prevention, diagnosis, and therapeutic management of cancer are becoming increasingly genetically based. Therefore, to ensure competency in oncology nursing practice at all levels, nurses must incorporate an understanding of the underlying biology of carcinogenesis and the molecular rationale underlying strategies to prevent, diagnose, and treat cancer.
UI - 12165453
AU - Morerio C; Calvari V; Rosanda C; Porta S; Gambini C; Panarello C
TI - XY female with a dysgerminoma and no mutation in the coding sequence of the SRY gene.
SO - Cancer Genet Cytogenet 2002 Jul 1;136(1):58-61
AD - Divisione di Ematologia ed Oncologia Pediatrica, Istituto Giannina Gaslini, Largo G. Gaslini 5, 16147 Genova, Italy.
We report a 46,XY 11-year-old girl with pure gonadal dysgenesis who developed a dysgerminoma. The testis-determining gene SRY, a candidate for sex reversal, whose alterations seem to correlate with dysgerminoma, was analyzed and found to be normal; its coding sequence was negative for deletions and mutations. DMRT-1 gene mapping on 9p and DAX-1 on Xp21 were also normal. These results suggest the involvement of other genes in sex reversal and call into question the putative relationship between SRY alterations and dysgerminoma.
UI - 11938448
AU - Nedelcu R; Liede A; Aube J; Finch A; Kwan E; Jack E; Narod SA; Randall
TI - S; Hugel L; Clark K BRCA mutations in Italian breast/ovarian cancer families.
SO - Eur J Hum Genet 2002 Feb;10(2):150-2
UI - 12144816
AU - Aktas D; Guney I; Alikasifoglu M; Yuce K; Tuncbilek E; Ayhan A
TI - CYP1A1 gene polymorphism and risk of epithelial ovarian neoplasm.
SO - Gynecol Oncol 2002 Aug;86(2):124-8
AD - Department of Genetics, Hacettepe University Medical School, 06100, Sihhiye, Ankara, Turkey. firstname.lastname@example.org
OBJECTIVE: Gene-environment interactions have been the focus of a number of recent studies of the occurrence of human cancers, and an association between the risk and the CYP1A1*3 polymorphism has been noticed for several cancers. Previous studies suggest that estrogens are involved in the etiology of ovarian cancer. The cytochrome P450 1A1 (CYP1A1) gene polymorphism may play role in the development of epithelial ovarian neoplasm by detoxification of polycyclic hydrocarbons and other compounds and the concentration of estrogens and their metabolites. Therefore, we assessed the association of CYP1A1 gene polymorphism in patients with epithelial ovarian neoplasm in the Turkish populations through a case-control study. METHODS: Using an allele-specific polymerase chain reaction (PCR)-based method, CYP1A1*3 polymorphism, in exon 7 of the gene, was analyzed in 117 epithelial ovarian neoplasm patients and 202 control subjects. RESULTS: The CYP1A1 Ile/Val genotype significantly increased the risk for patients with epithelial ovarian neoplasm (OR 5.7, 95% CI 3.34-9.76). Furthermore, there were statistical differences in the distribution of CYP1A1 Val/Val genotype among all patients (OR 5.85, 95% CI 2.40-14.25). In other words, the presence of the Val allele significantly increased the risk of epithelial ovarian neoplasm. Among benign tumors, the frequency of Ile/Val and Val/Val genotypes was found to be statistically significant with an ORs of 6.01 and 4.38 (95% CI 2.61-13.84 and 1.04-18.38, respectively). In the benign serous ovarian tumors, patients with Ile/Val and Val/Val revealed a 7.2- and 10.5-fold higher risk of having ovarian carcinoma (95% CI 2.22-23.40 and 2.16-51.19), respectively. In the benign mucinous ovarian carcinoma patients, the frequency of Ile/Val was found to be statistically significant with an OR of 5.15 (95% CI 1.75-15.16). However, no patient with Val/Val genotype was observed in this group and no statistical distribution was performed. Among borderline tumors, CYP1A1 Ile/Val genotype significantly increased the risk for patients (OR 5.15, 95% CI 1.75-15.16). However, only one patient was observed with the Val/Val allele and the frequency of this genotype was not found to be statistically different with an OR of 2.50 (95% CI 0.27-22.64). Among ovarian cancer patients, there were statistically differences in the distribution of CYP1A1 Ile/Val and Val/Val genotypes (OR 5.73, 95% CI 3.04-10.76; and OR 7.42, 95% CI 2.80-19.66), suggesting that patients carrying these genotypes were at increased risk for ovarian carcinoma. In serous carcinoma, patients with CYP1A1 Ile/Val and Val/Val revealed a 6.5- and 10-fold higher risk of having ovarian cancer (OR 7.09, 95% CI 3.30-15.22; and OR 8.77, 95% CI 2.83-27.14). In mucinous carcinoma, patients with CYP1A1 Ile/Val and Val/Val also revealed a 5.4 and 10.5 times higher risk of having ovarian cancer. There were no statistical significance in the distribution of Val allele among endometroid-type cancer patients. CONCLUSIONS: Our data, although based on a small number of subjects, suggest that variant alleles of CYP1A1 gene in ovarian epithelial cells, directly or through other components, may contribute to initiation of ovarian carcinogenesis.
UI - 12144818
AU - Hefler LA; Ludwig E; Lampe D; Zeillinger R; Leodolter S; Gitsch G;
TI - Koelbl H; Tempfer CB Polymorphisms of the endothelial nitric oxide synthase gene in ovarian cancer.
SO - Gynecol Oncol 2002 Aug;86(2):134-7
AD - Department of Obstetrics and Gynecology, University of Vienna Medical School, Vienna, Austria.
OBJECTIVE: The free radical nitric oxide is known to be critically involved in ovarian carcinogenesis by inducing apoptosis and by mediating various cytostatic and cytotoxic effects, but also by promoting growth, invasion, and metastasis. METHODS: We investigated two polymorphisms (exon 7 Glu298Asp and a 27-bp repeat in intron 4) of the gene encoding endothelial nitric oxide synthase (Nos3) in 130 patients with ovarian cancer, 26 patients with borderline ovarian cancer, and 133 healthy age-matched Caucasian women using PCR and pyrosequencing, respectively. RESULTS: Genotypes and allelic frequencies did not differ between patients with ovarian cancer and controls. Within the ovarian cancer group, however, the presence of at least one mutant allele of intron 4 was associated with advanced tumor stage and positive lymph node involvement, but not with tumor grading. The presence of the mutant allele of exon 7 was not associated with the investigated clinicopathological parameters. No correlation with patients' overall and disease-free survival was ascertained. CONCLUSIONS: We are the first to report on Nos3 polymorphisms in ovarian cancer. Allelic variation within intron 4 of Nos3 is associated with an advanced tumor stage and positive lymph node involvement in ovarian cancer.
UI - 12144824
AU - Kamazawa S; Kigawa J; Kanamori Y; Itamochi H; Sato S; Iba T; Terakawa N
TI - Multidrug resistance gene-1 is a useful predictor of Paclitaxel-based chemotherapy for patients with ovarian cancer.
SO - Gynecol Oncol 2002 Aug;86(2):171-6
AD - Department of Obstetrics and Gynecology, Tottori University School of Medicine, Yonago, 683-8504, Japan.
OBJECTIVE: The objective of this study was to determine the relationship between multidrug resistance and sensitivity to paclitaxel (PTX) in ovarian cancer. METHODS: We used human ovarian adenocarcinoma cell lines, KF, a PTX-resistant cell line (KFTx), SK-OV-3, and KOC7c. Additionally, 27 patients with ovarian cancer who had residual disease were examined. All patients underwent postoperative chemotherapy consisting of 175 mg/m(2) PTX and area under curve (AUC) 5 carboplatin. The sensitivity of the cells to PTX or cisplatin (CDDP) was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. mRNA expression of multidrug resistance gene-1 (MDR-1) and multidrug resistance-associated protein-1 (MRP-1) and MRP-2 was determined by reverse transcription-polymerase chain reaction. beta-Tubulin polymerization and Bcl-2 phosphorylation were examined by Western blot analysis. RESULTS: Compared with KF, the IC(50) to PTX was 5.5-fold higher for KFTx, 0.3-fold for SK-OV-3, and 52.1-fold for KOC7c. The IC(50) to CDDP was 0.7-, 4.2-, and 5.8-fold, respectively. Expression of the MDR-1 gene was clearly observed in KFTx and KOC7c. Expression of MRP-1 was observed in SK-OV-3 and KOC7c. Expression of MRP-2 was detected only in KOC7c. CDDP enhanced beta-tubulin polymerization induced by PTX in CDDP-sensitive cells. Bcl-2 phosphorylation appeared after exposure to IC(50) PTX in all cells. Twenty-one patients responded to chemotherapy and six did not. Expression of the MDR-1 gene for nonresponders was significantly higher than that for responders (260.0 +/- 191.6 vs 9.3 +/- 21.8). With the cutoff value of MDR-1 expression at 100, the predictive value for chemoresponse was 96%. Expression of the MRP-1 and MRP-2 genes did not differ between nonresponders and responders. CONCLUSION: MDR-1 gene expression may be a useful predictor for PTX-based chemotherapy.
UI - 12151180
AU - Werness BA; DiCioccio RA
TI - Transitional cell ovarian carcinoma in a BRCA1 mutation carrier.
SO - Obstet Gynecol 2002 Aug;100(2):385; discussion 385
UI - 12138242
AU - Hata K; Udagawa J; Fujiwaki R; Nakayama K; Otani H; Miyazaki K
TI - Expression of angiopoietin-1, angiopoietin-2, and Tie2 genes in normal ovary with corpus luteum and in ovarian cancer.
SO - Oncology 2002;62(4):340-8
AD - Department of Obstetrics and Gynecology, Shimane Medical University, Izumo, Japan. email@example.com
OBJECTIVE: The recent discovery of angiopoietin-1 (Ang1) and angiopoietin-2 (Ang2) has provided novel and important insights into the molecular mechanisms of blood vessel formation. Ang1 and Ang2 bind with similar affinity to the endothelial cell tyrosine kinase receptor Tie2. Our purpose was to assess the potential role of the Ang/Tie2 system in physiological and pathological angiogenesis in the ovary. METHODS: Ang1, Ang2, and Tie2 gene expression in 14 normal ovaries with corpus luteum (CL) and in 19 cases of ovarian cancer were analyzed by polymerase chain reaction of RNA after reverse transcription. The level of each gene expression was presented by the relative yield of each gene to the beta(2)-microglobulin gene, respectively. Furthermore, cellular distribution of Ang1 and Ang2 mRNA was examined by in situ hybridization, and localization of Tie2 was studied by immunochemistry. RESULTS: The Ang1, Ang2, and Tie2 gene expression in normal ovary with CL ranged from 0.18 to 1.06 (median 0.54), 0.31-2.64 (median 1.01), and 0.10-0.47 (median 0.20), respectively. The expression of these same genes in ovarian cancer ranged from 0.06 to 0.75 (median 0.14), 0.69-1.59 (median 1.12), and 0.04-0.35 (median 0.15), respectively. Ang1 gene expression in normal ovary with CL was significantly higher than that in ovarian cancer (p = 0.0004). The gene expression levels of Ang2 and Tie2 were statistically the same in both groups. There was a significant correlation between Ang1 gene expression and Tie2 gene expression in normal ovary with CL (r = 0.619, p = 0.018). No such significant correlation was found in ovarian cancer. Moreover, Ang2 gene expression showed no significant correlation with the Tie2 gene expression either in normal ovary with CL or in ovarian cancer. Transcripts for Ang1 were observed in CL cells and endothelial cells around CL, and in tumor cells and endothelial cells at the periphery of tumor invasion. Ang2 transcripts were expressed in the same patterns. Tie2 expression was positive primarily in the endothelial cells around CL and in those at the periphery of tumor invasion. CONCLUSION: Our results indicate that there is a difference in the Ang/Tie2 gene expression between physiological and pathological angiogenesis in the ovary. This finding may aid in the development of new therapeutic interventions for ovarian cancer. Copyright 2002 S. Karger AG, Basel
The above citations and abstracts reflect those newly added to CANCERLIT for the month and topic listed in the title. The citations have been retrieved from CANCERLIT using a predefined search strategy of indexed subject terms. Although the search strategy has been refined as best as possible, citations may appear that are not directly related to the topic, and occasionally relevant references may be omitted.
UI - 12084463
AU - Jackman AL; Melin CJ; Kimbell R; Brunton L; Aherne GW; Theti DS; Walton
TI - M A rationale for the clinical development of the thymidylate synthase inhibitor ZD9331 in ovarian and other solid tumours.
SO - Biochim Biophys Acta 2002 Jul 18;1587(2-3):215-23
AD - The Section of Medicine, Institute of Cancer Research, 15 Cotswold Road, Belmont, Surrey, Sutton, UK. firstname.lastname@example.org
ZD9331 is an antifolate drug that potently and specifically inhibits thymidylate synthase (TS). In contrast with TS inhibitors such as raltitrexed, it cannot be polyglutamated, leading to antitumour activity independent of folylpolyglutamyl synthetase (FPGS) activity.The growth inhibition IC50 values for ZD9331 and raltitrexed were determined for a panel of 18 human tumour cell lines, that included six colon and six ovarian. The colon lines largely displayed overlapping sensitivities to both drugs with only one of the six lines being drug resistant. In contrast, the ovarian cell lines displayed non-overlapping sensitivities with four being highly resistant to raltitrexed and only one was cross-resistant to ZD9331. Studies were undertaken to explain these results. The colon and ovarian cell lines were characterised for TS activity, and TS and FPGS mRNA expression. TS activity correlated with sensitivity to ZD9331 (r=0.50; p=0.097) and raltitrexed (r=0.74; p=0.0063). Provided the data from the highly drug-resistant cell lines (BE and 41 M) were omitted, TS mRNA expression levels also correlated with ZD9331 (r=0.77; p=0.013) and raltitrexed IC50 (r=0.84; p=0.0031). FPGS mRNA expression correlated with higher sensitivity to raltitrexed relative to ZD9331 (higher ZD9331/raltitrexed IC50 ratios) (r=0.62; p=0.048). Similarly, cell lines with IC50 ratios>median expressed a 1.8-fold higher median level of FPGS mRNA (p=0.0087) compared with those with ratios
UI - 12152163
AU - Hauptmann S; Denkert C; Koch I; Petersen S; Schluns K; Reles A; Dietel
TI - M; Petersen I Genetic alterations in epithelial ovarian tumors analyzed by comparative genomic hybridization.
SO - Hum Pathol 2002 Jun;33(6):632-41
AD - Institute of Pathology and Department of Gynecology and Obstetrics, Charite Hospital Berlin, Germany.
The genetic changes involved in the pathogenesis of ovarian carcinoma are not completely understood. To investigate this matter, we studied paraffin-embedded, microdissected tissue of 47 ovarian epithelial tumors (9 adenomas, 11 tumors of low malignant potential [LMP], 14 serous carcinomas, and 13 nonserous carcinomas) using comparative genomic hybridization (CGH). (The primary data used in this study are available at our CGH online tumor database at http://amba.charite.de/cgh.) Chromosomal imbalances were found in 1 serous adenoma and in 7 LMP tumors. In the latter the alterations appeared randomly and showed no overlap with alterations found in invasive carcinomas. Although the mean aberration number of low-grade serous carcinomas was comparable to LMP tumors, the imbalances of the former occurred with high incidence (>50%) and were found at different localizations. High-grade serous carcinomas had more than twice as much chromosomal imbalances as low-grade serous carcinomas and also had pronounced alterations. In serous carcinomas, gains were found on 3q, 6p, 7, 8q, and 20, and losses were found on 4q, 6q, 12q, 13q, and 16q. Comparing serous and nonserous carcinomas, the mean aberration number was comparable, but the number of high incidence changes was lower, and the most frequent imbalances were losses on 13q and gains on 20p. Overlapping alterations occurring in serous and nonserous carcinomas were gains on 3q and 6p, as well as losses on 4q. Chromosomal imbalances associated with poor prognosis of ovarian carcinomas were gains on 6p, 7q, and 13q and losses on 15q, 17p, 18q, and 21q. Our data indicate that serous LMP tumors and invasive carcinomas have different genetic aberrations, indicating that invasive carcinomas do not arise from preexisting serous LMP tumors. On the other hand, there are common genetic abnormalities in serous and nonserous carcinomas, suggesting that they have very early lesions in common but take different paths of further development. Copyright 2002, Elsevier Science (USA). All rights reserved.
UI - 11900873
AU - Lynch HT; Lynch JF
TI - Hereditary cancer: family history, diagnosis, molecular genetics, ecogenetics, and management strategies.
SO - Biochimie 2002 Jan;84(1):3-17
AD - Department of Preventive Medicine and Public Health, Creighton University School of Medicine, 2500 California Plaza, Omaha, Nebraska 68131, USA. email@example.com
The translation of knowledge about hereditary breast cancer and its improved control, as well as prevention through prophylactic surgery, has been significantly accelerated through the veritable explosive discoveries in molecular genetics inclusive of BRCA1 and BRCA2 germline mutations. Needed however, among the physician community, medical geneticists, and genetic counselors, is a raised level of knowledge about hereditary breast cancer syndromes. Particular attention needs to be given to their extant genotypic and phenotypic heterogeneity, their natural history, and foremost, the requirement of a sufficiently detailed family history, with knowledge as to how to interpret its significance so that hereditary cancer syndrome can be diagnosed, should it, in fact, exist in the particular family. Collectively, surveillance and management programs can then be developed for the patient and his or her high-risk relatives. We believe very firmly that this knowledge needs to be extended to the individual patient(s), first- and second-degree relatives so that they can benefit from this knowledge.
UI - 12160914
AU - Huiart L; Eisinger F; Stoppa-Lyonnet D; Lasset C; Nogues C; Vennin P;
TI - Sobol H; Julian-Reynier C Effects of genetic consultation on perception of a family risk of breast/ovarian cancer and determinants of inaccurate perception after the consultation.
SO - J Clin Epidemiol 2002 Jul;55(7):665-75
AD - Epidemiology and Social Sciences Unit (INSERM U379), Institut Paoli-Calmettes, 232 Bd Ste Marguerite, 13273 Marseille cedex 09, France.
The aim of this study was to assess the effects of cancer genetic consultations on women's perception of their family risk of breast/ovarian cancer, and to determine which factors were associated with an inaccurate perception after the consultation. A multicenter prospective survey was carried out on women (n = 397) attending cancer genetic clinics in France for the first time, in which the perceived family risk was measured both before and after the consultation, using self-administered questionnaires. The effects of the consultation on risk perception were significant among low (P <.001) and moderate risk women (P <.05). However, after the consultation, 76.3% of the "low"-risk women did not perceive their family as "low"-risk families, and 21.9% of the moderate-risk women were still definitely sure there was a genetic risk running in their family. The consultation did not affect the family risk perception of the high risk women (n = 171): the risk was thought to be very high both before (87.7%) and after (89.5%) the consultation (NS); however 10.5% of this group still perceived their family as being unlikely to be at risk after the consultation. In the low- and moderate-risk groups after multivariate adjustment, the inaccurate perceptions varied, depending on the clinics and on the psychosocial context of the consultation: they increased when the consultee was personally affected by cancer, and decreased when the consultee had a health occupation. Cancer genetic consultations had only marginal effects on the perception of family risk on the whole, although they were significant in the case of low- and moderate-risk women. The question arises as to whether a more comprehensive approach should be implemented and how to go about providing efficient cancer risk information in the context of health care systems.
UI - 12175530
AU - Marsh D; Zori R
TI - Genetic insights into familial cancers-- update and recent discoveries.
SO - Cancer Lett 2002 Jul 26;181(2):125-64
AD - Cancer Genetics, Kolling Institute of Medical Research and Department of Molecular Medicine, The University of Sydney, Royal North Shore Hospital, St. Leonards, NSW 2065, Sydney, Australia. firstname.lastname@example.org
While the vast majority of cancers are believed to occur sporadically, most forms of cancer, both adult and paediatric, have a hereditary equivalent. In the case of adult malignancies, these include hereditary breast and ovarian cancer and syndromes such as the multiple endocrine neoplasias types 1 and 2 characterised by specific tumours of the endocrine gland system. In the case of paediatric malignancies, these include syndromes such as retinoblastoma and Wilms tumour. In a little over a single decade, we have seen a tremendous increase in the knowledge of the primary genetic basis of many of the familial cancer syndromes. The majority of familial syndromes are inherited as autosomal dominant traits including hereditary colon cancer and familial malignant melanoma, however, the genetics behind autosomal recessive disorders such as Bloom syndrome and Fanconi anaemia are also being elucidated. A third mode of inheritance less well understood in the setting of familial cancer is that of imprinting recently observed in a subset of families with inherited paraganglioma. In this review, we discuss 31 genes inherited in an autosomal dominant manner associated with 20 familial cancer syndromes. Genes inherited in an autosomal recessive manner linked to familial cancer syndromes are also discussed. The identification of genes associated with familial cancer syndromes has in some families enabled a 'molecular diagnosis' that complements clinical assessment and allows directed cancer surveillance for those individuals determined to be at-risk of disease.
UI - 11933205
AU - Liede A; Jack E; Hegele RA; Narod SA
TI - A BRCA1 mutation in Native North American families.
SO - Hum Mutat 2002 Apr;19(4):460
AD - University of Toronto and Sunnybrook & Women's College, Health Sciences Centre, Toronto, Canada. email@example.com
Germline mutations in the BRCA1 (MIM 113705) and BRCA2 (MIM 600185) genes have been identified for breast and ovarian cancer families of diverse ethnic backgrounds. To date, there have been no reports of Native North American families with mutations in BRCA1 or BRCA2. Here we report two families of aboriginal descent both with the same BRCA1 alterations (1510insG, 1506A>G). The families represent two aboriginal Canadian tribes (Cree and Ojibwe), although a common ancestral origin is likely. This is the first evidence of a BRCA1 mutation specific to aboriginal peoples of North America. Copyright 2002 Wiley-Liss, Inc.
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