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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Loss of DNA sequences within human chromosomal band 7q31.2 is frequently observed in a number of different solid tumors including breast, prostate, and ovarian cancer. This chromosomal band also contains the common fragile site, FRA7G. Many of the common fragile sites occur within chromosomal regions that are frequently deleted during tumor formation but their precise position, relative to the chromosome breakpoints and deletions, has not been defined for the majority of the fragile sites. Because the frequency of expression of FRA7G is low, we analyzed the expression of FRA7G in a chromosome 7-only somatic cell hybrid (hamster-human). YAC clones defining a contig spanning 7q31.2 were then used as FISH probes against metaphase spreads prepared from the hybrid cells after aphidicolin induction. This analysis quickly revealed whether a specific YAC clone mapped proximal, distal, or actually spanned the region of decondensation/breakage of FRA7G. By using this approach, we have identified several overlapping YAC clones that clearly span FRA7G. Interestingly, these clones map precisely to the common region of LOH in breast cancer and prostate cancer. In addition, the MET oncogene is contained within the three YACs that span FRA7G.
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PMID:Fish mapping of YAC clones at human chromosomal band 7q31.2: identification of YACS spanning FRA7G within the common region of LOH in breast and prostate cancer. 949 27

The beclin 1 (BECN1) gene encodes a 60-kDa coiled-coil protein that interacts with the prototypic apoptosis inhibitor Bcl-2. Previous studies indicate that beclin 1 maps to a region approximately 150 kb centromeric to BRCA1 on chromosome 17q21 that is commonly deleted in breast, ovarian, and prostate cancer. The complete cDNA sequence of beclin 1 encodes a 2098-bp transcript, with a 120-bp 5' UTR, 1353-bp coding region, and 625-bp 3' UTR. Hybridization screening of a human genomic PAC library identified PAC 452O8, which contains the complete beclin 1 gene. Determination of the exon-intron structure of beclin 1 reveals 12 exons, ranging from 61 to 794 bp, which extend over 12 kb of the human genome. FISH analysis of human breast carcinoma cell lines using PAC 452O8 as probe identified allelic beclin 1 deletions in 9 of 22 cell lines. Sequencing of genomic DNA from 10 of these cell lines revealed no mutations in coding regions or splice junctions. Additionally, Northern blot analysis of 11 cell lines did not identify any abnormalities in beclin 1 transcripts. These results indicate that human breast carcinoma cell lines frequently contain allelic deletions of beclin 1, but not beclin 1 coding mutations.
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PMID:Cloning and genomic organization of beclin 1, a candidate tumor suppressor gene on chromosome 17q21. 1039

Cancer of the prostate remains poorly characterized cytogenetically. This is due in part to methodological problems and in part to the paucity of radical prostatectomies, until now the main source of material for cytogenetic analyses. We have improved existing techniques for the culturing of prostatic neoplasms removed by radical prostatectomy or sampled by ultrasound-guided needle biopsy. Successful short-term cultures were obtained from all 10 prostatectomy samples and from all 10 ultrasound-guided needle biopsies, always with a pure epithelial morphology. Of the 19 cases yielding a sufficient number of high-quality metaphases for chromosome banding analysis, the single atypical epithelial hyperplasia had a normal karyotype, whereas both prostatic intraepithelial neoplasias and 12 of 16 (75%) invasive carcinomas were shown to have clonal abnormalities. Ten of the 12 (83%) karyotypically abnormal invasive carcinomas presented structural chromosomal rearrangements. A recurrent deletion, del(10)(p13), was seen in three tumors; in one of them the terminal nature of the deletion was confirmed by two-color FISH. A del(17)(p11) was seen in one PIN lesion, but since the analysis of exons 4-8 of the TP53 tumor suppressor gene revealed no mutations, there probably was no inactivation of the second TP53 allele. Our study thus leads to the following main conclusions. First, better culturing methods allow the detection of abnormal karyotypes in a much higher percentage of prostatic neoplasms than has hitherto been possible. Second, ultrasound-guided needle biopsies of prostatic neoplasms are a sufficient source of material for cytogenetic analysis. Third, a terminal deletion of the short arm of chromosome 10, del(10)(p13), seems to identify a subgroup of prostatic cancer.
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PMID:High frequency of clonal chromosome abnormalities in prostatic neoplasms sampled by prostatectomy or ultrasound-guided needle biopsy. 1082 6

We have developed an alternative multicolor karyotyping technique based on multiplex fluorescence in situ hybridization (M-FISH) and our own optical device with a specific filter set. The most innovative part of our development is the use of interspersed polymerase chain reaction (IRS-PCR) painting probes that show an R-band pattern simultaneous to the combinatorial labeling. This allows us not only to recognize the origin of chromosomal fragments, but to identify the breakpoints as well. We have used this technique to analyze seven cell lines: four prostate cancer cell lines (CA-HPV-10, LNCaP, DU145, and PC3), and three normal transformed epithelial prostate cell lines (PNT1B, PNT2, and PZ-HPV-7). In order to validate our IRS-PCR multiplex FISH (IPM-FISH) technique and to complement the results, we applied comparative genomic hybridization (CGH) and FISH analysis, showing good correlation with the IPM-FISH results. To date, molecular and cytogenetic studies have identified several chromosomal regions that are altered in human prostate cancer; several candidate genes have been suggested. However, reliable markers for predicting the aggressiveness of early prostate cancer are not yet available. Our results show several common, unbalanced rearrangements in the cell lines. These rearrangements are similar to regions already implicated in prostate cancer, validating these cell lines as a good model system.
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PMID:IPM-FISH, a new M-FISH approach using IRS-PCR painting probes: application to the analysis of seven human prostate cell lines. 1113 31

Prostate cancer is the most common cancer in males in the United States, yet the etiology of this disease is still poorly understood. In previous work from our laboratory, one or more deleted regions were found in prostate tumors distal to the breast and ovarian cancer susceptibility gene (BRCA1) on chromosome 17. This suggested that genes at 17q21 may play a pivotal role in prostate cancer progression, and there may be new tumor suppressor genes at this locus. We now present a physical map built with P1, P1 artificial chromosome, and bacterial artificial chromosome clones encompassing a DNA sequence anchored by multiple STS markers. The analysis of prostate tumors indicated an 85-kb novel commonly deleted interval flanked by D17S1184-D17S183-D17S1203-D17S1860, which is at least 470 kb distal to the BRCA1 gene. Fifty-four of 126 prostrate cancer cases (43%) showed a deletion by a direct FISH technique using P1 probes in this region. Searching with clone end sequences in the sequence database BLAST, the deleted clone covered genomic DNA sequence that contained upstream binding factor (UBF), EPB3 genes, SHCL1, ASB-4-like sequence, and acidic protein-like sequence. PCR for the ESTs confirmed that these genes or ESTs are within the deletion region. Our results will be helpful for finding candidate tumor suppressor genes in prostate cancer.
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PMID:A common deletion at chromosomal region 17q21 in sporadic prostate tumors distal to BRCA1. 1117 Jul 49

Recent studies have identified several chromosome regions that are altered in primary prostate cancer and prostatic carcinoma cell lines. These targeted regions may harbor genes involved in tumor suppression. We used multiplex fluorescence in situ hybridization (M-FISH) to screen for genetic rearrangements in four prostate cancer cell lines, LNCaP, LNCaP.FCG, DU145, and PC3, and compared our results with those recently obtained using spectral karyotyping (SKY). A number of differences was noted between abnormalities characterized by SKY and M-FISH, suggesting variation in karyotype evolution and characterization by these two methodologies. M-FISH analysis showed that hormone-resistant cell lines (DU145 and PC3) contained many genetic alterations (> or =15 per cell), suggesting high levels of genetic instability in hormone-refractory prostate cancer. Most chromosome regions previously implicated in prostate cancer were altered in one or more of these cell lines. Several specific chromosome aberrations were also detected, including a del(4)(p14) and a del(6)(q21) in the hormone-insensitive cell lines, a t(1;15)(p?;q?) in LNCaP, LNCaP, and PC3, and a i(5p) in LNCaP.FCG, DU145, and PC3. These clonal chromosome abnormalities may pinpoint gene loci associated with prostate tumourigenesis, cancer progression, and hormone sensitivity.
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PMID:The use of multicolor fluorescence technologies in the characterization of prostate carcinoma cell lines: a comparison of multiplex fluorescence in situ hybridization and spectral karyotyping data. 1117 1

Recently developed molecular cytogenetic techniques for karyotyping are providing new and important insights regarding the chromosomal changes that occur in solid tumors. We used multiplex-FISH to analyze four adenocarcinoma cell lines, PC-3, PPC-1, ALVA-31, and ALVA-41, in which the characterization of a large number of rearranged chromosomes was partially or substantially inconclusive by G-banding. Although the original descriptions of these lines depict them as distinct entities established from different patients, this study demonstrates that these four lines share numerous, highly rearranged chromosomes, strongly supporting the conclusion that they are derived from the same patient material. Our analysis indicates that PPC-1, ALVA-31, and ALVA-41 were derived from PC-3 through mechanisms involving clonal progression represented by sequential changes and clonal diversion represented by differing patterns of changes. Extensive cellular heterogeneity was detected in all four lines, and most rearrangements included segments derived from multiple chromosomes. Each line also showed a set of unique derivative chromosomes. However, a limited number of metaphase cells (approximately 10) was analyzed for each line, and numerous single-cell abnormalities were detected in all of them. Therefore, it is plausible that the number of clonal, shared, and/or unique rearrangements has been underestimated. These cell lines have been utilized as models for understanding the biology of prostate cancer and reportedly differ in their cell physiology. Rather than detracting from their value, a complete understanding of the interrelationships of these lines to one another may provide the opportunity to define the molecular changes that have led to their individual malignant phenotypes.
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PMID:Karyotypic similarity identified by multiplex-FISH relates four prostate adenocarcinoma cell lines: PC-3, PPC-1, ALVA-31, and ALVA-41. 1143 21

Metastasis is responsible for most deaths from cancer. Currently, little is known about the early genetic events in the metastatic evolution. Here we describe the application of a newly developed strategy for an in-depth characterization of genomic changes in micrometastatic cells. Unique tumor cell lines were established from bone marrow of patients with cancer of the prostate and analyzed by multiplex-FISH (M-FISH) and array CGH. M-FISH revealed that the occult disseminated cells were characterized by very complex numerical and structural aberrations. Many of these aberrations resulted in chromosomal gains and losses, such as losses of 8p, 13q, and 18q and gains of 8q, 9q, 20, and the X chromosome, which are typically observed in prostate cancer. Array CGH allowed an unprecedented high-resolution assessment of copy number changes, pinpointing commonly gained or lost regions, which should narrow down the identification of regions critically involved in metastasis. Thus, occult micrometastatic cells are now amenable to detailed analyses of their genome. Markers for prognosis and treatment decisions can now be established.
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PMID:High-resolution genomic profiling of occult micrometastatic tumor cells. 1250 44

Mechanisms underlying prostate cancer (CaP) initiation and progression are poorly understood. A chromosomal instability mechanism leading to the generation of numerical and structural chromosomal changes has been implicated in the preneoplastic and neoplastic stages of CaP. Telomere dysfunction is one potential mechanism associated with the onset of such instability. To determine whether there was alteration in telomere length and chromosome number, 15 paraffin-embedded prostatectomy specimens were investigated using quantitative peptide nucleic acid (PNA) FISH analysis of representative foci of carcinoma, putative precancerous lesions (high-grade prostatic intraepithelial neoplasia, HPIN) and nondysplastic prostate epithelium. A significant decrease in telomere length was shown in both HPIN and CaP in comparison with normal epithelium. In addition, elevated rates of aneusomy suggested that increased levels of chromosomal aberrations were associated with decreased telomere length. Moreover, multiple foci of HPIN were shown to have a heterogeneous overall reduction of telomere length. This reduction was more evident in the histologic regions of the prostate containing CaP. Such observations lend support to the hypothesis that telomere erosion may be a consistent feature of CaP oncogenesis and may also be associated with the generation of chromosomal instability that characterizes this malignancy.
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PMID:Evidence of multifocality of telomere erosion in high-grade prostatic intraepithelial neoplasia (HPIN) and concurrent carcinoma. 1267 3

In the course of the last decades, dramatic advances in the field of molecular biology have greatly increased our knowledges regarding the chromosomal aberrations associated with both hereditary and sporadic tumours. The development of new techniques (RELF, FISH, CGH, cDNA array analysis and functional oncogenetics, etc.) has provided powerful new tools for identification of onco- and oncosuppressor predisposing-genes. The most logical consequence of genetic research is the gene-therapy by directing treatment to the site of the chromosomal defect. The implementation of gene-directed technologies (gene-replacement or augmentation, antisense, interfering small -RNAs, etc.) into clinical practice stands as a model of translational research from laboratory to bedside. Prevention and therapy may be widely influenced by the experience of these techniques. On the other hand, some chemoprevention trials are carried out in subjects with hereditary risk for prostate cancer. The paper aims to outline the advances of genetics in urogenital hereditary tumours on the basis of a review of the literature in this field.
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PMID:[Inheritance in neoplastic urogenital pathology]. 1461 Apr 36


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