Download or read book Identifying and Isolating Breast Cancer Associated Genes on Chromosomes written by and published by . This book was released on 1999 with total page 90 pages. Available in PDF, EPUB and Kindle. Book excerpt: A region on human chromosome ii at plS.S is associated with breast cancer. Metastasis and poor outcome are the cancer phenotypes associated with this region. This is a study to identif

Download or read book Identifying and Isolating Breast Cancer Associated Genes on Chromosome 11 written by and published by . This book was released on 1998 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: There is a region on human chromosome ii at pl 5.5 that has been associated with the breast cancer phenotype. These results were obtained by loss of heterozygosity (LOM) studies in breast tumors. Metastasis and poor outcome are the cancer phenotypes associated with lip' 5.5. Since breast cancer patients usually do not die as a result of the primary tumor, but from the progression to a metastatic phenotype, we have embarked on a study to identify% the gene(s) responsible on lip15.5. We have constructed a detailed physical map across the region, participated in sequencing the region, generated a transcript map across the region and have begun to access the genes in this region as candidates for tumor suppressor genes. The candidate region has been reduced to 400 kb and contains about 4-6 potential genes. We have cloned the region and the molecular characterization has begun. Interestingly, the 11p15.5 .5 region has been shown to be located in an imprinted domain. We have evidence to suggest preferential 11pl 5.5 maternal loss in breast tumors suggesting that breast cancer in this region has an imprinting component. We have cloned the homologous imprinted region from the mouse and are testing for imprinted expression in fetal and adult tissues including mammary gland.

Download or read book Molecular Biology of the Cell written by and published by . This book was released on 2002 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Mammography and Beyond written by National Research Council and published by National Academies Press. This book was released on 2001-07-23 with total page 311 pages. Available in PDF, EPUB and Kindle. Book excerpt: Each year more than 180,000 new cases of breast cancer are diagnosed in women in the U.S. If cancer is detected when small and local, treatment options are less dangerous, intrusive, and costly-and more likely to lead to a cure. Yet those simple facts belie the complexity of developing and disseminating acceptable techniques for breast cancer diagnosis. Even the most exciting new technologies remain clouded with uncertainty. Mammography and Beyond provides a comprehensive and up-to-date perspective on the state of breast cancer screening and diagnosis and recommends steps for developing the most reliable breast cancer detection methods possible. This book reviews the dramatic expansion of breast cancer awareness and screening, examining the capabilities and limitations of current and emerging technologies for breast cancer detection and their effectiveness at actually reducing deaths. The committee discusses issues including national policy toward breast cancer detection, roles of public and private agencies, problems in determining the success of a technique, availability of detection methods to specific populations of women, women's experience during the detection process, cost-benefit analyses, and more. Examining current practices and specifying research and other needs, Mammography and Beyond will be an indispensable resource to policy makers, public health officials, medical practitioners, researchers, women's health advocates, and concerned women and their families.

Download or read book Isolation of a Breast Cancer Tumor Suppressor Gene from Chromosome 3p written by and published by . This book was released on 1998 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Loss of tumor suppressor genes (TSGs) represent critical molecular events in the development and progression of breast cancer. Based on loss of heterozygosity (LOH) studies as well as direct cytogenetic studies of breast tumors, one or more TSGs likely resides on the short arm of chromosome 3 (3p) and appears to be involved in nearly 50% of breast cancers. Four distinct regions within 3p P12, P14, P21 (PROXIMAL) AND P21 (DISTAL) undergo recurrent deletions in human carcinomas and are the most likely sites for a breast cancer TSG. In our previous Progress Reports and publications, we demonstrated recurrent homozygous deletion or rearrangement in breast cancer cell lines involving 3p14. The critical region was cloned and sequenced which led to the identification of several putative exons. We determined that 3p14 is subject to a high degree of genomic instability which is ongoing in some cases. We have also made substantial progress in evaluating other 3p regions for involvement in breast cancer, as originally proposed. This has included the 3p21.31 and 3p21.33 homozgyous deletion regions as well as the interval between. In addition, we have discovered a novel patched-related gene which resides in a region of frequent amplification in breast tumors.

Download or read book Isolation of Genes from Chromosome Region Ip31 Involved in the Development of Breast Cancer written by and published by . This book was released on 1999 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Loss of heterozygosity (LOH) involving the p31 region of chromosome 1 has been reported as one of the most frequent genetic changes in human breast cancer. LOH is generally considered a mechanism for exposing recessive mutations in genes critical for tumorigenesis. We have begun creating a contiguous array of bacterial artificial chromosome (BAC) clones spanning the minimum region in Ip31 defined by LOH studies. These clones will facilitate the search for genes from the region which can be tested for mutations in breast tumors. One such gene, TTC4, has been identified, cloned and characterized. This gene contains a tetratricopeptide repeat motif which has been implicated in protein-protein binding and one member of this extended family of genes has been implicated in liver tumorigenesis.

Download or read book Breast Cancer Genes Identified by Loss of Heterozygosity written by Roy Riblet and published by . This book was released on 1998 with total page 15 pages. Available in PDF, EPUB and Kindle. Book excerpt: We are working to develop a novel genomic subtraction method to rapidly identify all chromosomal regions that undergo Loss of Heterozygosity (LOH) in breast cancer. LOH is a major mechanism in the genomic alteration that transforms a normal cell into an unregulated tumor cell. The identification of all regions of LOH will identify causative genes and gene interactions and will yield new understanding of the etiology and pathogenesis of breast cancer and lead to new approaches to detection and treatment. We designed several genomic subtraction methods to isolate enriched populations of DNA fragments representing LOH regions in individual breast cancer cell lines. Our approach exploits the minor degree of DNA sequence heterogeneity expected between the members of each chromosome pair. Genomic subtraction requires presence/absence differences, and we transform the DNAs to create such differences.

Download or read book Isolation of Breast Tumor Suppressor Genes from Chromosome 11p written by Pratima Karnik and published by . This book was released on 2001 with total page 43 pages. Available in PDF, EPUB and Kindle. Book excerpt: In published studies, we have shown that chromosome 11p15.5 exhibits loss of heterozygosity (LOH) in ^60% of breast tumors, and that there is a significant correlation between lip LOH, lymphatic invasion and aggressive metastatic disease. Our data suggests that chromosome 11p15.5 harbors a tumor/metastasis suppressor gene. An intriguing candidate gene that we have mapped to the tumor/metastasis suppressor locus on chromosome 11p15.5 is Integrin-linked Kinase (ILK). ILK is a newly identified ankyrin-repeat containing serine/threonine kinase that binds to the cytoplasmic domains of both 81 and the 83 integrins. Here, we present evidence that the Integrin-Linked Kinase (ILK) gene maps to the commonly deleted chromosome 11p15.5 and suppresses malignant growth of human breast cancer cells both in vitro and in vivo. ILK is expressed in normal breast tissue but-not in metastatic breast cancer cell lines or in advanced breast cancers. Transfection of wild-type ILK into the MDA-MBA35 mammary carcinoma cells potently suppressed their growth and invasiveness in vitro, and reduced the cells' ability to induce tumors and metastasize in athymic mice. Conversely, expression of the ankyrin repeat or catalytic domain mutants of ILK failed to suppress the growth of these cells. Growth suppression by ILK is not due to apoptosis but is mediated by its ability to block cell cycle progression in the G1 phase. These findings directly demonstrate that ILK deficiency facilitates neoplastic growth and suggest a novel role for the ILK gene in tumor suppression.

Download or read book Cloning Human Chromosome 17 Genes Candidate Genes for BRCA1 written by Cheng-Chi Lee and published by . This book was released on 1997 with total page 17 pages. Available in PDF, EPUB and Kindle. Book excerpt: Our research interest is focused on the identification of genes from chromosome 17. The isolation of genes transcribed from chromosome 17 will provide candidates for the proposed sporadic breast cancer genes and genes for other human disorders. The ability to isolate genes in a chromosome specific manner provides simultaneous identification of the expressed sequence and a chromosomal location. Our approach identifies expressed sequences by reciprocal probing of arrayed cDNA libraries and a chromosome specific cosmid library. To date from the cDNAs isolated from human chromosome 17 we have identified two very important gene & One gene, which encode a coactosin like protein (CLI) and maps to l7pl 1.2 has been demonstrated by us and our collaborators to be involved in the Smith-Magenis Syndrome, a neuro-muscular disorder. A second gene which encodes a putative transcription factor has been demonstrated by my laboratory to be a key gene in the mammalian circadian rhythm pathway. This gene which we have named RIGUl could initiate molecular studies into hypotheses that the responsiveness of patients to chemotherapy display circadian patterns.

Download or read book Isolation of Breast Tumor Suppressor Genes from Chromosome Lip written by and published by . This book was released on 1999 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: We have previously shown that chromosome lip 15.5 exhibits loss of heterozygosity (LOH) in 60% of breast tumors, and that there is a significant correlation between lip LOH, lymphatic invasion and aggressive metastatic disease. Our data suggests that chromosome lip 15.5 harbors a metastasis suppressor gene. An intriguing candidate gene that we have mapped to the metastasis suppressor locus on chromosome lip15.5 is integrin-linked kinase (ILK). ILK is a newly identified ankyrin-repeat containing serine/threonine kinase that binds to the cytoplasmic domains of both Beta 1 and the Beta 3 integrins. Cell-cell and cell-matrix interactions are important prerequisites of the metastatic process and appear to be modulated by cell adhesion receptors called integrins. There is a growing body of evidence suggesting that variations in the expression of these molecules can have a profound effect on tumor biology. In preliminary experiments, we have provided evidence that Integrin-linked kinase expression is down-regulated in primary breast tumors and in cell lines derived from metastatic breast tumors. We have shown that ILK overexpression inhibits the growth of the highly metastatic breast cancer cell line MDA-MB-435. In addition, ILK overexpression stimulates the levels of the growth suppressing integrin alpha5Beta1 and inhibits the levels of alphavBeta3, a growth promoting integrin. These studies suggest that ILK is a breast cancer metastasis suppressor gene.

Download or read book Identification of BRCA1 and 2 Other Tumor Suppressor Genes on Chromosome 17 Through Positional Cloning written by and published by . This book was released on 2000 with total page 81 pages. Available in PDF, EPUB and Kindle. Book excerpt: The overall goal of this project is to identify genes involved with the development and progression of breast cancer. This goal has remained unchanged since the start of the project, however the discovery of BRCA1 in 1994 together with technological advances in gene expression profiling has influenced our strategy to achieve this goal. In the early part of the project our search for tumor suppressor genes was directed by genetic or LOH mapping strategies followed by positional cloning of candidate genes. As we proposed in our revised statement of work (SOW), we have now focused our efforts entirely on microarray-based comparisons to identify breast cancer related genes. Our laboratory has gained access to this technology through collaboration with Molecular Dynamics and now we have established microarray spotting and scanning systems with over 40,000 minimally redundant sequence-verified human cDNA clones. Once candidate genes have been identified, they will be further characterized using a retroviral-based conditional expression system to assess changes in characteristics pertaining to morphology and growth rate by culturing human breast epithelial cells in an extracellular matrix.

Download or read book Identification of Chromosomes Alterations in Primary Breast Cancer Using Premature Chromosome Condensation written by and published by . This book was released on 2000 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Site-specific chromosome alterations have led to the identification of numerous genes directly involved in hematologic malignancies and selected solid tumors. Recognition of recurrent chromosome translocations are particularly informative because they can lead directly to the cloning and identification of genes which are altered in neoplasms. We hypothesize that, as been shown in other human tumors, early clinical breast cancers have site-specific, clonal chromosomal translocations which have not been identified previously. We are developing a new method, premature chromosome condensation (PCC), using mitotic Xenopus extracts that will allow us to obtain G-banded karyotypes from primary, uncultured breast cancer specimens. We have made such extracts and are optimizing conditions for use. We are also using a sensitive new technique termed spectral karyotyping (SKY), to identify site-specific, recurrent clonal chromosomal translocations in these PCC-induced karyotypes of primary breast cancer specimens. The problems in application at this point are technical and being addressed. Following the identification of recurrent, site specific chromosome alterations and particularly translocations in primary breast cancer, future investigations would target our long-term goal of identifying the genes directly involved at these chromosomal breakpoints.

Download or read book Identification and Localization of Genes Which Restore Senescence in Breast Cancer Cells written by and published by . This book was released on 1999 with total page 41 pages. Available in PDF, EPUB and Kindle. Book excerpt: Using a combination of positional and functional cloning, we have mapped SEN 16 to a lO0xb region at 16q24.3. Intact, normal human chromosome 16, when transferred into immortal human (MCF& SKBR-3) and rat (LA7 & NMU) mammary tumor cells by microcell mediated chromosome transfer (MMCT) restored senescence to these cells. Moreover, transfer of a fragment of chromosome 16 containing 16q23-qter also induced senescence to these tumor cells. Continuous culture of the senescent cells in selection media gave rise to revertant cells which have parental cell growth phenotype and have lost the region of the introduced chromosome that harbors the senescence gene. Analysis of these revertant clones with previously mapped chromosome 16-specific markers placed the senescence gene within a 3-7 cm region at 16q24.3. Three overlapping Yeast-Artificial-Chromosome (YAC) clones spanning this region were obtained. Transfer of one of these YACs, 792El (360 Kb), restored senescence in MCF' and LA7 cells while another YAC containing a portion of chromosome 6 did not alter the growth characteristics of these cells. To further map SENl6, a partial Bacterial-Artificial-Chromosome (BAC) contig was created spanning the YAC 792E1. Experiments are in progress to identify a BAC that harbors SENl 6 and to further clone and characterize, this gene.

Download or read book Genome Stability written by Igor Kovalchuk and published by Academic Press. This book was released on 2021-07-17 with total page 762 pages. Available in PDF, EPUB and Kindle. Book excerpt: Genome Stability: From Virus to Human Application, Second Edition, a volume in the Translational Epigenetics series, explores how various species maintain genome stability and genome diversification in response to environmental factors. Here, across thirty-eight chapters, leading researchers provide a deep analysis of genome stability in DNA/RNA viruses, prokaryotes, single cell eukaryotes, lower multicellular eukaryotes, and mammals, examining how epigenetic factors contribute to genome stability and how these species pass memories of encounters to progeny. Topics also include major DNA repair mechanisms, the role of chromatin in genome stability, human diseases associated with genome instability, and genome stability in response to aging. This second edition has been fully revised to address evolving research trends, including CRISPRs/Cas9 genome editing; conventional versus transgenic genome instability; breeding and genetic diseases associated with abnormal DNA repair; RNA and extrachromosomal DNA; cloning, stem cells, and embryo development; programmed genome instability; and conserved and divergent features of repair. This volume is an essential resource for geneticists, epigeneticists, and molecular biologists who are looking to gain a deeper understanding of this rapidly expanding field, and can also be of great use to advanced students who are looking to gain additional expertise in genome stability. A deep analysis of genome stability research from various kingdoms, including epigenetics and transgenerational effects Provides comprehensive coverage of mechanisms utilized by different organisms to maintain genomic stability Contains applications of genome instability research and outcomes for human disease Features all-new chapters on evolving areas of genome stability research, including CRISPRs/Cas9 genome editing, RNA and extrachromosomal DNA, programmed genome instability, and conserved and divergent features of repair

Download or read book Cloning Human Chromosome 17 Genes written by and published by . This book was released on 1995 with total page 15 pages. Available in PDF, EPUB and Kindle. Book excerpt: Our research interest is focused on the development of new strategies to identify genes from chromosome 17. The isolation of genes transcribed from chromosome 17 will provide candidates for the proposed sporadic breast and ovarian cancer genes. We have recently reported a method for the isolation of chromosome specific cDNAs using high density arrayed cDNA and chromosome specific cosmid libraries. The ability to isolate genes in a chromosome specific manner provides simultaneous identification of the expressed sequence and a chromosomal location. This new technology identifies expressed sequences by reciprocal probing of arrayed cDNA libraries and a chromosome specific cosmid library. We have used these resources to identify 1794 clones from the Los Mamos chromosome 17 cosmid library using probes generated from a placental cDNA library. So far, we have isolated and characterized 42 cDNAs to chromosome 17. Several of these cDNAs mapped to the region 17p13, while 14 other cDNAs mapped to the region of 17q12-22. Recent studies have demonstrated that in some sporadic breast cancer there are loss of heterozygosity (LOH) in these regions of human chromosome 17.

Download or read book Identification of Tumor Suppressor Genes in Breast Cancer by Insertional Mutagenesis and Functional Inactivation written by YAN. SU and published by . This book was released on 1998 with total page 19 pages. Available in PDF, EPUB and Kindle. Book excerpt: The development and progression of cancer result from multiple genetic changes accumulated in the cells. The identification of tumor suppressor genes inactivated and proto-oncogenes activated in mammary epithelial cells is essential to understand the genetic basis of breast cancer and is a prerequisite for development of strategies for prevention, diagnosis, and treatment. In breast cancer, loss of heterozygosity (LOH) was detected frequently on chromosome 17 and other chromosomes, suggesting unrecognized tumor suppressor genes. We are applying the novel retroviral-tagging strategy to identify the genes using chromosome 17-suppressed (independent of p53 and BRCAl) breast cancer cell lines. In contrast to the parental tumorigenic cell line CAL51, the suppressed sublines CAL/17-3 and CAL/17-5 display retard growth in flasks, no growth in soft-agar culture and athymic nude mice. In this annual report, we present preparation of biological materials including cell culture, isolation of DNA and RNA, construction of cDNA library and packaging retrovirus particles. In order to provide antisense and mutant proteins to inhibit activities of tumor suppressor genes, poly-(A)+RNA was isolated from the suppressed subline CAL17-3 and used to construct the library. We are now in the process to package cDNA library into retrovirus particles for transduction.

Download or read book Identification of Genetic Markers of the Invasive Phenotype in Human Breast Cancer written by Peter H. Watson and published by . This book was released on 2000 with total page 45 pages. Available in PDF, EPUB and Kindle. Book excerpt: Invasion is a crucial component of the complex process of metastasis that marks the transition of breast cancer from local to life threatening disease. The approach we have taken to identify the molecular pathology underlying the onset of invasion, is to apply a combined microdissection and molecular approaches to a unique tissue bank resource. This enables us to isolate mRNA and directly compare gene expression profiles from pathologically defined regions of DCIS and early invasive tumor cells. We have microdissected and identified a number of genes that show differential expression between DCIS and invasive components (in 5 tumors by subtraction hybridization and 8 tumors by membrane filter cDNA array techniques), as well as between low and high grade DCIS. We have also pursued 3 specific genes, previously unexplored in relation to breast cancer, that show patterns of differential expression consistent with a role in the process of invasion - Psoriasin (S100A7), Lumican, (a small leucine-rich proteoglycan) and Angio-Associated Migratory Protein (AAMP). We conclude that our approach is productive in identifying novel genes that are previously unexplored in relation to early breast tumor progression and believe that these may provide markers of progression to invasive disease.