- Cancer Types
Information about risk, prevention, screening, symptoms, diagnosis, treatment, and support for all cancers Cancer A to Z - Cancer Treatment
Cancer Treatment
Information about cancer treatment, including surgery, chemotherapy, radiation therapy, clinical trials, proton therapy, complementary medicine, and cutting edge technologies.
- Risk and Prevention
- Cancer Drugs
- Support
Support
Ways for cancer patients and caregivers to cope with cancer, side effects, nutrition, general cancer support issues, grief/end of life issues, and shared survivor's experiences.
- Healthcare Professionals
- Clinical Trials
My Patient Treatment Binder
OncoLink Blogs
What's My Cancer Risk?
OncoPilot: Navigating Your Cancer Journey
Community Events Calendar
OncoLink eNews
Abramson Cancer CenterNCI CANCERLIT® Search: Hereditary Ovarian Cancer - January 2002
National Cancer Institute®
Last Modified: January 1, 2002
Table of Contents
1
UI - 11248061
AU - Levy-Lahad E; Lahad A; Eisenberg S; Dagan E; Paperna T; Kasinetz L;
TI -
Catane R; Kaufman B; Beller U; Renbaum P; Gershoni-Baruch R
A single nucleotide polymorphism in the RAD51 gene modifies cancer risk
in BRCA2 but not BRCA1 carriers.
SO - Proc Natl Acad Sci U S A 2001 Mar 13;98(6):3232-6
AD - Medical Genetics Unit, Shaare Zedek Medical Center and Hebrew
University/Hadassah Medical School, P.O. Box 3235, Jerusalem 91031,
Israel. lahad@szmc.org.il
BRCA1 and BRCA2 carriers are at increased risk for both breast and
ovarian cancer, but estimates of lifetime risk vary widely, suggesting
their penetrance is modified by other genetic and/or environmental
factors. The BRCA1 and BRCA2 proteins function in DNA repair in
conjunction with RAD51. A preliminary report suggested that a single
nucleotide polymorphism in the 5' untranslated region of RAD51 (135C/G)
increases breast cancer risk in BRCA1 and BRCA2 carriers. To investigate
this effect we studied 257 female Ashkenazi Jewish carriers of one of
the common BRCA1 (185delAG, 5382insC) or BRCA2 (6174delT) mutations. Of
this group, 164 were affected with breast and/or ovarian cancer and 93
were unaffected. RAD51 genotyping was performed on all subjects. Among
BRCA1 carriers, RAD51-135C frequency was similar in healthy and affected
women [6.1% (3 of 49) and 9.9% (12 of 121), respectively], and RAD-135C
did not influence age of cancer diagnosis [Hazard ratio (HR) = 1.18 for
disease in RAD51-135C heterozygotes, not significant]. However, in BRCA2
carriers, RAD51-135C heterozygote frequency in affected women was 17.4%
(8 of 46) compared with 4.9% (2 of 41) in unaffected women (P = 0.07).
Survival analysis in BRCA2 carriers showed RAD51-135C increased risk of
breast and/or ovarian cancer with an HR of 4.0 [95% confidence interval
1.6-9.8, P = 0.003]. This effect was largely due to increased breast
cancer risk with an HR of 3.46 (95% confidence interval 1.3-9.2, P =
0.01) for breast cancer in BRCA2 carriers who were RAD51-135C
heterozygotes. RAD51 status did not affect ovarian cancer risk. These
results show RAD51-135C is a clinically significant modifier of BRCA2
penetrance, specifically in raising breast cancer risk at younger ages.
2
UI - 11434389
AU - Campos B; Diez O; Cortes J; Domenech M; Pericay C; Alonso C; Baiget M
TI -
Conditions for single-strand conformation polymorphism (SSCP) analysis
of BRCA1 gene using an automated electrophoresis unit.
SO - Clin Chem Lab Med 2001 May;39(5):401-4
AD - Servei de Genetica, Hospital de la Santa Creu i Sant Pau, Barcelona,
Spain.
The single-strand conformation polymorphism procedure has been applied
in routine testing for hereditary diseases and cancer. However,
temperature, running time, gel composition, fragment length, etc. can
influence its sensitivity. Mutation detection in the clinical setting
depends on the development of automated technology, especially for large
genes such as the breast cancer gene BRCA1. We analysed DNA samples with
BRCA1 mutations in an automated system (GenePhor System;
Amersham-Pharmacia Biotech, Uppsala, Sweden). The concentrations of DNA
template and PCR primers, the effect of chilling after denaturation, and
the temperature and time of the electrophoresis were investigated. All
band-shifts were detected by electrophoresis at 5 degrees C for 2 h 15
min. Concentrations of DNA and samples used in the PCR did not affect
the SSCP pattern, but chilling the PCR product in ice after denaturation
was required. The type and position of mutation in the fragments did not
influence the probability of a mobility shift, although SSCP analysis
was more sensitive for fragments shorter than 350 bp. This automated
SSCP method meets the requirements of fast turnaround and sensitivity
and can be readily adapted to the screening of large genes such as
BRCA1.
3
UI - 11474658
AU - Mahavni V; Kim SC; Benda TA; Sanders L; Buller RE
TI -
The androgen receptor and DXS15-134 markers show a high rate of
discordance for germline X chromosome inactivation.
SO - J Med Genet 2001 Jul;38(7):474-8
4
UI - 11444200
AU - Garrett AP; Lee KR; Colitti CR; Muto MG; Berkowitz RS; Mok SC
TI -
k-ras mutation may be an early event in mucinous ovarian tumorigenesis.
SO - Int J Gynecol Pathol 2001 Jul;20(3):244-51
AD - Laboratory of Gynecologic Oncology, Division of Gynecologic Oncology,
Department of Obstetrics and Gynecology, Brigham and Women's Hospital
and Harvard Medical School, 75 Francis Street, Boston, Massachusetts,
USA.
We explored the possible pathogenetic pathway for mucinous ovarian
tumorigenesis by examining the k-ras mutational patterns in ovarian
mucinous tumors (OMTs) with benign, borderline, and invasive epithelium
in which the different types of mucinous epithelium are in close
proximity. Sixteen patients with ovarian mucinous borderline tumors
(OMBTs) and 4 patients with grade 1 ovarian mucinous adenocarcinomas
(OMCs) were selected for the presence of a single histologic section
which contained a clear "transition" zone from benign mucinous
epithelium to borderline mucinous epithelium, and in four cases, to
invasive epithelium. A PixCell II Laser Capture Microscope was used to
microdissect and retrieve benign, borderline, and invasive epithelium
separately from the 20 OMTs. Normal ovarian stroma from the same
histologic section in each case was also microdissected and retrieved
for use as a control. k-ras mutations were detected in these samples by
PCR-SSCP analysis followed by direct PCR cycle sequencing. k-ras
mutations were found in 8/16 (50%) of the OMBTs and 2/4 (50%) of the
grade 1 OMCs. In 6 of these 10 cases (4 in OMBTs, 2 in grade 1 OMCs),
the same k-ras mutation was found in both the benign and borderline (and
invasive) regions. In 3 cases in which k-ras mutations were identified,
the mutation was found in either the benign or borderline tissue samples
alone, and in one case, two distinct mutations were found. No k-ras
mutations were identified in the normal ovarian stroma. The presence of
a k-ras mutation in adjacent benign and borderline regions of a single
OMT may suggest a progression in the development of OMTs from benign to
borderline and grade 1 OMCs. k-ras mutations, when they occur, are
likely early genetic changes but may not alone be sufficient for
malignant transformation of ovarian epithelium.
5
UI - 11462239
AU - Jakubowska A; Gorski B; Byrski T; Huzarski T; Gronwald J; Menkiszak J;
TI -
Cybulski C; Debniak T; Hadaczek P; Scott RJ; Lubinski J
Detection of germline mutations in the BRCA1 gene by RNA-based
sequencing.
SO - Hum Mutat 2001 Aug;18(2):149-56
AD - Department of Genetics and Pathology, Pomeranian Academy of Medicine,
Polabska, Poland. aniaj@r1.pam.szczecin.pl
BRCA1 mutation detection is expensive and has sensitivity limitations,
which might at least partially be overcome by RNA-based sequencing.
There are claims that RNA tests are unreliable due to differential
splicing, exon skipping, or nonsense-mediated mRNA decay that results in
either the absence or low expression of mRNA harboring mutations. The
major aim of this study was to determine if the application of specific
high temperature annealing primers can assure high sensitivity of
detection of BRCA1 sequence alterations by cDNA sequencing. The study
group comprised 21 Polish cancer families with aggregations of breast
and/or ovarian cancer. We detected mutations in 10 out of 21 unrelated
patients. These were: nucleotide substitutions (c.309T>C; c.300T>G);
nucleotide insertions (c.5382insC) three cases; nucleotide deletions
(c.4154delA) one case, (c. 185delAG) one case, (c.3819delGTAAA) two
cases; and the deletion of the entire sequence of exon 22, one case. In
addition, we identified three transcript variants resulting from
alternative splice sites affecting the last six nucleotides of exon 1a
(GTAAAG), and the first three nucleotides (CAG) of exon 8 and exon 14.
In all cases these were cDNA heterozygous changes. Two of these splice
site changes have not been previously described. Sequencing of genomic
DNA "exon by exon" did not result in the detection of any additional
abnormalities. The sensitivity of our analyses was sufficient to
reliably detect mutations without the necessity of tissue culturing to
obtain enough template cDNA for analysis. Copyright 2001 Wiley-Liss,
Inc.
6
UI - 11462242
AU - Baudi F; Quaresima B; Grandinetti C; Cuda G; Faniello C; Tassone P;
TI -
Barbieri V; Bisegna R; Ricevuto E; Conforti S; Viel A; Marchetti P;
Ficorella C; Radice P; Costanzo F; Venuta S
Evidence of a founder mutation of BRCA1 in a highly homogeneous
population from southern Italy with breast/ovarian cancer.
SO - Hum Mutat 2001 Aug;18(2):163-4
AD - Dipartimento di Medicina Sperimentale e Clinica "G. Salvatore",
Universita degli Studi di Catanzaro "Magna Graecia", Italy.
Several genes have been involved in the pathogenesis of hereditary
breast/ovarian cancer (BOC), but mutations in the BRCA1 gene are by far
the most recurrent. In this study, we report the identification of a
founder mutation in a geographically and historically homogeneous
population from Calabria, a south Italian region. A screening performed
on 24 patients from unrelated families highlighted the high prevalence
of a 5083del19 alteration in the BRCA1 gene, which accounts for 33% of
the overall gene mutations. The same mutation was also detected in 4
patients, all of Calabrian origin, referred to us by research centres
from the north of Italy. Allelotype analysis, performed on probands and
unaffected family members revealed the presence a common allele,
therefore suggesting a founder effect due to a common ancestor. Our
findings underscore the importance of ethnic background homogeneity in
patients' selection and highlight the usefulness of founder mutations as
a potential tool for optimisation of preclinical diagnosis in gene
carriers and therapeutic approaches in affected individuals. Copyright
2001 Wiley-Liss, Inc.
7
UI - 11499690
AU - Srivastava A; McKinnon W; Wood ME
TI -
Risk of breast and ovarian cancer in women with strong family histories.
SO - Oncology (Huntingt) 2001 Jul;15(7):889-902; discussion 902, 905-7,
911-13
AD - Division of Hematology and Oncology, University of Vermont College of
Medicine, Burlington 05401, USA.
Assessing the risk of breast and ovarian cancer starts with obtaining a
complete and accurate family history. This can reveal evidence of
inherited cancer risk. The highest risk of cancer is associated with
germ-line abnormalities in several genes, including BRCA1, BRCA2, and
TP53. Moderate-risk genes associated with syndromes that are inherited
in an autosomal dominant pattern (such as Cowden's disease, hereditary
non-polyposis colorectal cancer, Muir-Torre syndrome, and Peutz-Jeghers
syndrome) exhibit lower penetrance and thus less risk of breast and/or
ovarian cancer. Low-risk genes likely require significant environmental
exposure, and although they are associated with the lowest risk of
cancer, they account for more cancer than high- and moderate-risk genes.
Lifetime risks for breast or ovarian cancer can be estimated. The Gail
and Claus models, the more widely utilized models for calculation of
lifetime breast cancer risk, are discussed. Models are also available
for determining the likelihood of finding a BRCA1/2 mutation (the
BRCAPRO and Myriad models). Appropriate candidates for testing include
affected individuals who are most likely to have a hereditary form of
cancer. Testing should proceed only after a thorough discussion of the
risks, benefits, and limitations of testing. Risk-reducing options are
available to women with a strong family history of breast and ovarian
cancer. These options include high-risk screening, chemoprevention, and
prophylactic surgery.
8
UI - 11501783
AU - Kaya H; Evans MF; Ekicioglu G; Tuzlali S; Kullu S; Foster C
TI -
Antimetastasis gene expression and numerical chromosomal abnormalities
of chromosomes 1 & 17 in serous tumours of the ovary.
SO - Eur J Gynaecol Oncol 2001;22(3):240-2
AD - Marmara University, School of Medicine, Department of Pathology,
Istanbul, Turkey.
OBJECTIVE(S): The aim of this study was to examine the expression of the
antimetastasis gene nm23 and numerical changes on chromosome 1 and 17 in
ovarian tumours. METHODS: In this study 20 serous cystadenocarcinomas,
ten borderline and five benign tumours were analysed for expression of
the nm23 antimetastasis gene by immunohistochemistry and for numerical
chromosomal abnormalities of chromosomes 1 and 17 by interphase
cytogenetics. RESULTS: Strong intracytoplasmic immunoreactivity with the
antimetastasis gene was observed in late stage carcinomas but not in
benign or borderline tumours or in lymph node metastases. Numerical
abnormalities were only observed in carcinomas. CONCLUSION(S): These
sets of data are consistent with the majority of benign and borderline
tumours lacking invasive potential. Odds Ratio (OR) assessment indicates
that the presence of numerical aberrations correlates with
immunopositivity.
9
UI - 11499181
AU - Memarzadeh S; Berek JS
TI -
Advances in the management of epithelial ovarian cancer.
SO - J Reprod Med 2001 Jul;46(7):621-9; discussion 629-30
AD - Division of Gynecologic Oncology, University of California-Los Angeles
School of Medicine, 27-136 CNS, 10833 Le Conte Avenue, Los Angeles, CA
90095-1740, USA.
More than 23,400 new cases of ovarian cancer and 13,900 deaths are
expected in the United States this year. Epithelial ovarian cancer is
the most common histologic type of ovarian malignancy. Although there
have been advances in the chemotherapeutic treatment of ovarian cancer,
the five year survival of women with advanced-stage disease is 25-30%.
Because the disease is typically asymptomatic until the disease has
metastasized and because effective screening strategies are not
unavailable, 70-75% of women present with advanced-stage disease. Of
ovarian cancer cases, 90-95% are sporadic and 5-10% associated with
germ-line mutations, including BRCA1 and BRCA2. Known risk factors for
ovarian cancer include nulliparity and a strong family history of
ovarian cancer. The use of oral contraceptives is known to decrease the
risk of ovarian cancer: five years of use will decrease the risk by 50%.
The staging of ovarian cancer (according to the International Federation
of Obstetrics and Gynecology) requires surgical exploration. Determining
the extent of disease is essential to appropriate management. Survival
in patients with metastatic disease is improved in those who undergo
optimal primary cytoreductive surgery. Adjuvant chemotherapy is
recommended in patients with high-risk, early-stage disease and all
patients with advanced-stage disease. Standard chemotherapy is a
combination of paclitaxel and carboplatin. Selected patients with
recurrent disease can undergo secondary cytoreductive surgery.
Second-line chemotherapy for patients who initially respond to
paclitaxel and carboplatin and who have a prolonged disease
progression-free intervals (longer than 12 months) can be re-treated
with either drug or both. Those whose responses to initial therapy were
less successful can be treated with other chemotherapeutic agents--e.g.,
liposomal doxorubicin, topotecan, etoposide, gemcitabine or taxotere.
10
UI - 11529589
AU - Phillips KA
TI -
Current perspectives on BRCA1- and BRCA2-associated breast cancers.
SO - Intern Med J 2001 Aug;31(6):349-56
AD - Department of Haematology and Medical Oncology, Peter MacCallum Cancer
Institute, Melbourne, Victoria, Australia.
PhillipsKelly@petermac.unimelb.edu.au
The identification of two breast cancer predisposition genes, BRCA1 and
BRCA2, in the mid-1990s has led to a better understanding of the
molecular pathogenesis of hereditary breast cancer and to a new era in
breast cancer research. The present article reviews the current state of
knowledge regarding the biology of BRCA1 and BRCA2, the cancer risks
associated with carrying a pathogenic mutation in either of these genes
and the possible genetic and environmental risk modifiers. The
phenotypes of BRCA1- and BRCA2-associated hereditary breast cancers are
reviewed. Research into BRCA1- and BRCA2-associated breast cancer is in
its infancy and much remains to be learned, particularly about modifiers
of genetic risk and the clinical implications of carrying a mutation in
one of these two genes. Australia has an excellent research
infrastructure in place, through the Australian Breast Cancer Family
Study and the Kathleen Cuningham Foundation Consortium for Research into
Familial Breast Cancer, to contribute substantially to future research
in this area.
11
UI - 11572989
AU - Paige AJ; Taylor KJ; Taylor C; Hillier SG; Farrington S; Scott D;
TI -
Porteous DJ; Smyth JF; Gabra H; Watson JE
WWOX: a candidate tumor suppressor gene involved in multiple tumor
types.
SO - Proc Natl Acad Sci U S A 2001 Sep 25;98(20):11417-22
AD - Imperial Cancer Research Fund (ICRF) Medical Oncology Unit, Western
General Hospital, Crewe Road, Edinburgh EH4 2XU, United Kingdom.
a.paige@icrf.icnet.uk
We previously reported the construction of a P1-derived artificial
chromosome (PAC) contig encompassing a set of homozygous deletions of
chromosome 16q23-24.1 found in primary ovarian tumor material and
several tumor cell lines. Using these PAC clones in a cDNA selection
experiment, we have isolated a Sau3A fragment homologous to the WWOX
transcript (GenBank accession no. ) from normal human ovarian surface
epithelial (HOSE) cells. We demonstrate the homozygous deletion of WWOX
exons from ovarian cancer cells and three different tumor cell lines. We
also identify an internally deleted WWOX transcript from a further
primary ovarian tumor. In three of these samples the deletions result in
frameshifts, and in each case the resulting WWOX transcripts lack part,
or all, of the short chain dehydrogenase domain and the putative
mitochondrial localization signal. Sequencing revealed several missense
polymorphisms in tumor cell lines and identified a high level of single
nucleotide polymorphism (SNP) within the WWOX gene. This evidence
strengthens the case for WWOX as a tumor suppressor gene in ovarian
cancer and other tumor types.
12
UI - 11578810
AU - Lin H; Morin PJ
TI -
A novel homozygous deletion at chromosomal band 6q27 in an ovarian
cancer cell line delineates the position of a putative tumor suppressor
gene.
SO - Cancer Lett 2001 Nov 8;173(1):63-70
AD - Laboratory of Cellular and Molecular Biology, Gerontology Research
Center, National Institute on Aging, NIH, 5600 Nathan Shock Drive,
Baltimore, MD 21224, USA.
Chromosomal band 6q27 is believed to contain a tumor suppressor gene
important in the development of several cancer types, including ovarian
cancer. However, repeated efforts to identify a tumor suppressor gene in
this region have been unsuccessful. Because homozygous deletions have
been useful in the positional cloning of a number of tumor suppressor
genes, we initiated a systematic search for such deletions in ovarian
cancer cell lines using 6q microsatellite markers. One of the cell
lines, OV167, was found to contain an 80 kb homozygous deletion
encompassing marker D6S193 at 6q27 but excluding nearby marker D6S297.
No known genes were present in the deleted region. Because the
homozygous deletion might affect the expression of nearby genes, we
analyzed the expression of the two closest known genes flanking the
deletion, RNASE6PL and RSK-3. The expression of these genes were
unaffected by the homozygous deletion, suggesting that the functional
target of the deletion is located between these two genes. A search of
the region against expressed sequence tag (EST) databases revealed that
it contained four sets of expressed sequences. The first expressed
sequences were derived from a LINE repetitive element and were
considered unlikely to represent a tumor suppressor gene. The other
expressed sequence tags identified did not show homology to known genes
and are currently being investigated. This data may significantly reduce
the magnitude of the search for the 6q tumor suppressor gene as it
suggests a small area as a prime target for investigation.
13
UI - 11583950
AU - Giordano TJ; Shedden KA; Schwartz DR; Kuick R; Taylor JM; Lee N; Misek
TI -
DE; Greenson JK; Kardia SL; Beer DG; Rennert G; Cho KR; Gruber SB;
Fearon ER; Hanash S
Organ-specific molecular classification of primary lung, colon, and
ovarian adenocarcinomas using gene expression profiles.
SO - Am J Pathol 2001 Oct;159(4):1231-8
AD - Department of Pathology, The University of Michigan, Ann Arbor, Michigan
48109-0054, USA. giordano@med.umich.edu
Molecular classification of tumors based on their gene expression
profiles promises to significantly refine diagnosis and management of
cancer patients. The establishment of organ-specific gene expression
patterns represents a crucial first step in the clinical application of
the molecular approach. Here, we report on the gene expression profiles
of 154 primary adenocarcinomas of the lung, colon, and ovary. Using
high-density oligonucleotide arrays with 7129 gene probe sets,
comprehensive gene expression profiles of 57 lung, 51 colon, and 46
ovary adenocarcinomas were generated and subjected to principle
component analysis and to a cross-validated prediction analysis using
nearest neighbor classification. These statistical analyses resulted in
the classification of 152 of 154 of the adenocarcinomas in an
organ-specific manner and identified genes expressed in a putative
tissue-specific manner for each tumor type. Furthermore, two tumors were
identified, one in the colon group and another in the ovarian group,
that did not conform to their respective organ-specific cohorts.
Investigation of these outlier tumors by immunohistochemical profiling
revealed the ovarian tumor was consistent with a metastatic
adenocarcinoma of colonic origin and the colonic tumor was a pleomorphic
mesenchymal tumor, probably a leiomyosarcoma, rather than an epithelial
tumor. Our results demonstrate the ability of gene expression profiles
to classify tumors and suggest that determination of organ-specific gene
expression profiles will play a significant role in a wide variety of
clinical settings, including molecular diagnosis and classification.
14
UI - 11584052
AU - Mills GB; Bast RC Jr; Srivastava S
TI -
Future for ovarian cancer screening: novel markers from emerging
technologies of transcriptional profiling and proteomics.
SO - J Natl Cancer Inst 2001 Oct 3;93(19):1437-9
15
UI - 11584061
AU - Mok SC; Chao J; Skates S; Wong K; Yiu GK; Muto MG; Berkowitz RS; Cramer
TI -
DW
Prostasin, a potential serum marker for ovarian cancer: identification
through microarray technology.
SO - J Natl Cancer Inst 2001 Oct 3;93(19):1458-64
AD - Department of Obstetrics, Gynecology, and Reproductive Biology, Brigham
and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
scmok@rics.bwh.harvard.edu
BACKGROUND: Screening biomarkers for ovarian cancer are needed because
of its late stage at diagnosis and poor survival. We used microarray
technology to identify overexpressed genes for secretory proteins as
potential serum biomarkers and selected prostasin, a serine protease
normally secreted by the prostate gland, for further study. METHODS: RNA
was isolated and pooled from three ovarian cancer cell lines and from
three normal human ovarian surface epithelial (HOSE) cell lines.
Complementary DNA generated from these pools was hybridized to a
microarray slide, and genes overexpressed in the cancer cells were
identified. Real-time quantitative polymerase chain reaction was used to
examine prostasin gene expression in ovarian cancer and HOSE cell lines.
Anti-prostasin antibodies were used to examine prostasin expression and
to measure serum prostasin by an enzyme-linked immunosorbent assay in 64
case patients with ovarian cancer and in 137 control subjects.
Previously determined levels of CA 125, an ovarian cancer marker, were
available from about 70% of all subjects. All statistical tests were
two-sided. RESULTS: Prostasin was detected by immunostaining more
strongly in cancerous ovarian epithelial cells and stroma than in normal
ovarian tissue. The mean level of serum prostasin was 13.7 microg/mL
(95% confidence interval [CI] = 10.5 to 16.9 microg/mL) in 64 case
patients with ovarian cancer and 7.5 microg/mL (95% CI = 6.6 to 8.3
microg/mL) in 137 control subjects (P<.001, after adjustment for the
subject's age, year of collection, and specimen quality). In 14 of 16
case patients with both preoperative and postoperative serum samples,
postoperative prostasin levels were statistically significantly lower
than preoperative levels (P =.004). In 37 case patients with nonmucinous
ovarian cancer and in 100 control subjects for whom levels of CA 125 and
prostasin were available, the combination of markers gave a sensitivity
of 92% (95% CI = 78.1% to 98.3%) and a specificity of 94% (95% CI =
87.4% to 97.7%) for detecting ovarian cancer. CONCLUSIONS: Prostasin is
overexpressed in epithelial ovarian cancer and should be investigated
further as a screening or tumor marker, alone and in combination with CA
125.
16
UI - 11586035
AU - Ozalp S; Yalcin OT; Gulbas Z; Tanir HM; Minsin T
TI -
Effect of cellular DNA content on the prognosis of epithelial ovarian
cancers.
SO - Gynecol Obstet Invest 2001;52(2):93-7
AD - Department of Gynecology and Obstetrics, Gynecologic Oncology Unit,
Osmangazi University School of Medicine, Eskisehir, Turkey.
OBJECTIVE: To assess the cellular DNA status of epithelial ovarian
cancers with regard to clinicopathological findings and its effect on
prognosis. MATERIALS AND METHODS: Twenty-six consecutive patients with a
diagnosis of epithelial ovarian cancer who had been treated by primary
surgery and six courses of platinum-based chemotherapy were enrolled in
this study. Second-look laparotomy (SLL) was performed in all cases
following confirmation of the clinical remission state. Surgical stage,
tumor grade, initial tumor volume, residual tumor volume,
histopathologic differentiation, and SLL findings were analyzed in
correlation with DNA ploidy and DNA index. DNA analysis was performed
via DNA flow cytometry through paraffin-embedded tissue specimens.
RESULTS: Of 26 patients, flow cytometric studies revealed 16 aneuploidy
cases (61.5%). DNA index values ranged from 1.1 to 1.82 (average 1.29
+/- 0.28). The flow cytometry coefficient of variation mean value was
set to 6.7. Taking the cutoff value of 1.2 for DNA indices, a fairly
good correlation was detected between DNA ploidy and DNA indices (p <
0.001). The aneuploidy incidence was found to be high in advanced and
poorly differentiated tumors (p < 0.05). There was statistically more
residual tumor volume in aneuploid tumors during primary cytoreductive
surgery and also higher recurrence rates following six courses of
chemotherapy compared with diploid tumors (p < 0.05). No significant
correlation was detected between the histopathologic subtypes and tumor
volume (p > 0.05). Residual tumor volumes were larger in cases with DNA
indices of 1.2 yielding higher residual tumor volume following surgery
and being in good correlation with SLL results (p < 0.05). The mean
survival rates of cases with aneuploid tumor and a DNA index of >1.2
were low compared to those with diploid tumors and DNA indices of <1.2
tumors (p < 0.05). CONCLUSION: DNA ploidy and DNA indices are important
prognosticators for malignant epithelial ovarian tumors. They should be
evaluated together with the patient's clinical status and other
prognostic factors. Copyright 2001 S. Karger AG, Basel
17
UI - 11590094
AU - Yeung KY; Ruzzo WL
TI -
Principal component analysis for clustering gene expression data.
SO - Bioinformatics 2001 Sep;17(9):763-74
AD - Computer Science and Engineering, Box 352350, University of Washington,
Seattle, WA 98195, USA. kayee@cs.washington.edu
MOTIVATION: There is a great need to develop analytical methodology to
analyze and to exploit the information contained in gene expression
data. Because of the large number of genes and the complexity of
biological networks, clustering is a useful exploratory technique for
analysis of gene expression data. Other classical techniques, such as
principal component analysis (PCA), have also been applied to analyze
gene expression data. Using different data analysis techniques and
different clustering algorithms to analyze the same data set can lead to
very different conclusions. Our goal is to study the effectiveness of
principal components (PCs) in capturing cluster structure. Specifically,
using both real and synthetic gene expression data sets, we compared the
quality of clusters obtained from the original data to the quality of
clusters obtained after projecting onto subsets of the principal
component axes. RESULTS: Our empirical study showed that clustering with
the PCs instead of the original variables does not necessarily improve,
and often degrades, cluster quality. In particular, the first few PCs
(which contain most of the variation in the data) do not necessarily
capture most of the cluster structure. We also showed that clustering
with PCs has different impact on different algorithms and different
similarity metrics. Overall, we would not recommend PCA before
clustering except in special circumstances.
18
UI - 11592838
AU - Rudginsky S; Siders W; Ingram L; Marshall J; Scheule R; Kaplan J
TI -
Antitumor activity of cationic lipid complexed with immunostimulatory
DNA.
SO - Mol Ther 2001 Oct;4(4):347-55
AD - Genzyme Corporation, Framingham, Massachusetts 01701, USA.
We previously reported that treatment of intraperitoneal tumors with
complexes of cationic lipid and noncoding plasmid DNA leads to the
development of a specific, cytotoxic T-cell response correlating with
the rejection of established tumor cells as well as subsequent tumor
re-challenge. Here, focusing on an intraperitoneal AB12 mesothelioma
model, we show that the anticancer effects of the lipid:DNA complex are
associated with DNA containing immunostimulatory CpG motifs. Complexes
prepared with cationic lipid and bacterial plasmid DNA, Escherichia coli
genomic DNA fragments, or synthetic immunostimulatory CpG
oligodeoxynucleotides provided a substantial survival benefit, whereas
eukaryotic DNA and methylated bacterial DNA had little or no therapeutic
activity. Alternative inflammatory stimuli such as thioglycolate,
poly(I:C), and incomplete or complete Freund's adjuvant failed to
reproduce the antitumor activity obtained with the lipid:DNA complex.
The innate immune response triggered by lipid:DNA complexes led to the
development of a systemic immune response against tumor cells that
allowed animals to reject tumors not only at the intraperitoneal
treatment site, but also at a distal subcutaneous site. These data
demonstrate that immunostimulatory DNA complexed with cationic lipid is
a potent inducer of innate and adaptive immune responses against tumor
cells and represents a potentially useful tool in the immunotherapy of
cancers for which tumor-associated antigens have not been identified.
19
UI - 11595686
AU - Reles A; Wen WH; Schmider A; Gee C; Runnebaum IB; Kilian U; Jones LA;
TI -
El-Naggar A; Minguillon C; Schonborn I; Reich O; Kreienberg R;
Lichtenegger W; Press MF
Correlation of p53 mutations with resistance to platinum-based
chemotherapy and shortened survival in ovarian cancer.
SO - Clin Cancer Res 2001 Oct;7(10):2984-97
AD - Department of Pathology, University of Southern California School of
Medicine, Los Angeles, CA 90033, USA.
PURPOSE: The p53 tumor suppressor gene plays a central role in cell
cycle regulation and induction of apoptosis. We analyzed p53 alterations
and their impact on response to chemotherapy and clinical outcome in
ovarian cancer patients. EXPERIMENTAL DESIGN: One hundred seventy-eight
ovarian carcinomas, snap frozen and stored at -80 degrees C, were
analyzed for mutations of the p53 gene (exons 2-11) by single-strand
conformation polymorphism and DNA sequencing and for p53 overexpression
by immunohistochemistry (monoclonal antibody DO7). RESULTS: p53
mutations were found in 56% (99 of 178) of the tumors, and 62% of these
were located in evolutionary highly conserved domains of the gene. Time
to progression and overall survival were significantly shortened in
patients with p53 mutations compared with wild-type p53 (P = 0.029 and P
= 0.014) and patients with mutations in highly conserved domains as
opposed to nonconserved domains or wild-type p53 (P = 0.010 and P =
0.007). p53 protein overexpression (>10% positively stained nuclei) was
found in 62% (110 of 178). Time to progression and overall survival were
shorter in cases with p53 overexpression (cutpoint, 10%: P = 0.071 and P
= 0.056) but only marginally significant. Resistance to adjuvant
cisplatin or carboplatin chemotherapy was significantly more frequent in
patients with p53 overexpression (P = 0.001) or p53 missense mutations
(P = 0.008) than patients with normal p53. CONCLUSIONS: p53 alterations
correlate significantly with resistance to platinum-based chemotherapy,
early relapse, and shortened overall survival in ovarian cancer patients
in univariate analysis. In multivariable analysis though, p53 was not an
independent prognostic factor.
20
UI - 11595708
AU - Sekine M; Nagata H; Tsuji S; Hirai Y; Fujimoto S; Hatae M; Kobayashi I;
TI -
Fujii T; Nagata I; Ushijima K; Obata K; Suzuki M; Yoshinaga M; Umesaki
N; Satoh S; Enomoto T; Motoyama S; Tanaka K; Japanese Familial Ovarian
Cancer Study Group
Mutational analysis of BRCA1 and BRCA2 and clinicopathologic analysis of
ovarian cancer in 82 ovarian cancer families: two common founder
mutations of BRCA1 in Japanese population.
SO - Clin Cancer Res 2001 Oct;7(10):3144-50
AD - Department of Obstetrics and Gynecology, Niigata University School of
Medicine, 1-757, Asahimachi-dori, Niigata City 951-8510, Japan.
We analyzed genetic alterations in BRCA1 and BRCA2 genes among 82
ovarian cancer families in Japan. The clinical characteristics of
BRCA-associated ovarian cancer patients were compared with cases
carrying no mutations as well as with population controls. Using a
direct sequencing method, 45 of the 82 ovarian cancer families were
found to carry BRCA1 or BRCA2 germ-line mutations (40 with BRCA1 and 5
with BRCA2). In 24 independent mutations of BRCA1, 5 recurrent mutations
were found and 2 of them, the L63X and Q934X mutations, were detected in
seven and eight independent families, respectively. In addition, 16
mutations of BRCA1 and 3 mutations of BRCA2 have never been described
previously. In consideration of clinicopathological features, there was
a significantly higher proportion of tumors with serous adenocarcinoma
and of cases of advanced stages in the BRCA1 or BRCA2 cases than in
those of the controls. On the other hand, there were no differences of
mean age at diagnosis between patients with BRCA1 or BRCA2 mutation and
those of the controls. Our results indicate that the features of
BRCA-associated ovarian cancer in Japan appear to be similar to those in
Western countries, and the L63X and Q934X mutations of BRCA1 appear to
be common founder mutations unique to the Japanese population.
21
UI - 11597388
AU - Verhoog LC; van den Ouweland AM; Berns E; van Veghel-Plandsoen MM; van
TI -
Staveren IL; Wagner A; Bartels CC; Tilanus-Linthorst MM; Devilee P;
Seynaeve C; Halley DJ; Niermeijer MF; Klijn JG; Meijers-Heijboer H
Large regional differences in the frequency of distinct BRCA1/BRCA2
mutations in 517 Dutch breast and/or ovarian cancer families.
SO - Eur J Cancer 2001 Nov;37(16):2082-90
AD - Division of Tumour Endocrinology, Department of Medical Oncology,
Cancer Types
Bone Cancer
Brain Tumors
Breast Cancer
Carcinoid Tumors
Endocrine System Cancers
Gastrointestinal Cancers
Gynecologic Cancers
Head and Neck Cancers
Leukemia
Lung Cancers
Lymphomas
Myelomas
Pediatric Cancers
Penile Cancer
Prostate Cancer
Sarcomas
Skin Cancers
Testicular Cancer
Thyroid Cancer
Urinary Tract Cancers
OncoLink Vet
Cancer Treatment
Biologic Therapy
Bone Marrow Transplants
Chemotherapy
Clinical Trials
Complementary Medicine
Gene Therapy
General Treatment Concerns
Hormone Therapy
PDT Center
Proton Therapy
Radiation Oncology
Surgical Oncology
Targeted Therapies
Vaccine Therapies
Cancer Support
Caregivers
Hospice Care and Bereavement
Nutrition and Cancer
Sexuality & Fertility
Side Effects
Support
Survivorship
Exercise and Cancer
Cancer Resources
Cancer News
OncoLink University
Nurses' Notes
Conferences
Newly Diagnosed Patients
Causes and Prevention
Legal and Financial Information for Patients
LGBT Resources
NCI Resources
Global Resources
Cancer Resource List
Resources for Young Adults
OncoLink Media Library
OncoLink TV
Book, Music and Video Reviews
Ask the Experts
Brown Bag Chat
Tracy's Corner
About OncoLink
About OncoLink
Giving to OncoLink
Contact Information
Usage Policy
Editorial Board
How to Partner with OncoLink
Link to OncoLink
Mission Statement
