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Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A COMPLEX SITUATION: Carcinomas of unknown primary site (CUP) represent at least 3% of cancers in adults. This group is heterogenic and difficult to treat, the central element of which is permanent discussions between the physician and the anatomopathologist. SPECIFIC CLINICAL FORMS: The physician must rapidly identify certain entities of good prognosis or particular treatment: cervical lymph node metastases, axillary adenopathies from occult breast cancer, primary papillary peritoneal carcinomatosis, and median line syndrome. OTHER THAN IN THESE SITUATIONS: Present recommended diagnosis strategy is limited and non-invasive (histological review with immunohistochemistry, measurement of alphaFP, beta-HCG, PSA, chest X ray, mammography, tomography of abdomen and pelvis). Positron emission scintigraphy would merit further evaluation.
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PMID:[Diagnostic management of inaugurable metastases]. 1287 30

The nature of genetic alterations in bilateral breast cancer (BBC) associated with the distinctive development of a second primary tumor or a metastatic lesion is not clearly established. In this study, patterns of promoter methylation and gene copy number changes were assessed for their utility in the distinction of two types of BBC (synchronous and metachronous). Seven cases of synchronous and five cases of metachronous breast cancer tissues were used in X chromosome inactivation assay to assess the methylation pattern of human androgen receptor gene. X chromosome inactivation assay alone did not provide enough information to distinguish the genetic origins of synchronous and metachronous BBC. When four pairs of paraffin-embedded BBC tissues were used in cDNA array-based CGH with placenta DNA as a reference, higher DNA copy number changes were observed from metachronous pairs (9.0%) than from synchronous pairs (3.1%). From the two cases of metachronous pairs tested, 44 genes were found to be commonly modulated in gene copy numbers in a cancer detected later.
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PMID:The pattern of gene copy number changes in bilateral breast cancer surveyed by cDNA microarray-based comparative genomic hybridization. 1465 65

Analysis of genomic DNA derived from cells and fresh or fixed tissues often requires whole genome amplification prior to microarray screening. Technical hurdles to this process are the introduction of amplification bias and/or the inhibitory effects of formalin fixation on DNA amplification. Here we demonstrate a balanced-PCR procedure that allows unbiased amplification of genomic DNA from fresh or modestly degraded paraffin-embedded DNA samples. Following digestion and ligation of a target and a control genome with distinct linkers, the two are mixed and amplified in a single PCR, thereby avoiding biases associated with PCR saturation and impurities. We demonstrate genome-wide retention of allelic differences following balanced-PCR amplification of DNA from breast cancer and normal human cells and genomic profiling by array-CGH (cDNA arrays, 100 kb resolution) and by real-time PCR (single gene resolution). Comparison of balanced-PCR with multiple displacement amplification (MDA) demonstrates equivalent performance between the two when intact genomic DNA is used. When DNA from paraffin-embedded samples is used, balanced PCR overcomes problems associated with modest DNA degradation and produces unbiased amplification whereas MDA does not. Balanced-PCR allows amplification and recovery of modestly degraded genomic DNA for subsequent retrospective analysis of human tumors with known outcomes.
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PMID:Balanced-PCR amplification allows unbiased identification of genomic copy changes in minute cell and tissue samples. 1515 23

Increasing evidence points at an important function of Vitamin D metabolites for growth regulation in various tissues, including MM. Using array CGH, amplification of 24-OHase was recently detected as a likely target oncogene of the amplification unit 20q13.2 in breast cancer cell lines and tumors. Additionally, amplification of 1alpha-OHase has been reported in human malignant glioma. Using immunohistochemistry, we have now detected nuclear Vitamin D receptor (VDR) immunoreactivity in primary cutaneous malignant melanoma (MM), indicating that Vitamin D metabolites may be of importance for the growth regulation in these tumors. Using Southern analysis, we have analyzed MM and metastases for evidence of amplification of 1alpha-OHase or 24-OHase genes. Our results do not support the hypothesis that amplification of 1alpha-OHase or 24-OHase genes may be of importance for pathogenesis or progression of MM.
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PMID:No evidence for amplification of 25-hydroxyvitamin D-1alpha-OHase (1alpha-OHase) or 1,25-dihydroxyvitamin D-24-OHase (24-OHase) genes in malignant melanoma (MM). 1522 66

The issue of whether multiple, ipsilateral or bilateral, breast carcinomas represent multiple primary tumours or dissemination of a single carcinomatous process has been difficult to resolve, especially for individual patients. We have addressed the problem by comparative genomic hybridisation analysis of 26 tumours from 12 breast cancer patients with multiple ipsilateral and/or bilateral carcinoma lesions. Genomic imbalances were detected in 25 of the 26 (96%) tumours. Using the genomic imbalances detected in these 26 lesions as well as those previously found by us in an independent series of 35 unifocal breast carcinomas, we compared a probabilistic model for likelihood of independence with unsupervised hierarchical clustering methodologies to determine the clonal relatedness of multiple tumours in breast cancer patients. We conclude that CGH analysis of multiple breast carcinomas followed by unsupervised hierarchical clustering of the genomic imbalances is more reliable than previous criteria to determine the tumours' clonal relationship in individual patients, that most ipsilateral breast carcinomas arise through intramammary spreading of a single breast cancer, and that most patients with bilateral breast carcinomas have two different diseases.
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PMID:Assessment of clonal relationships in ipsilateral and bilateral multiple breast carcinomas by comparative genomic hybridisation and hierarchical clustering analysis. 1526 23

Single nucleotide polymorphism (SNP) arrays were used to detect chromosomal regions with DNA copy number alterations. Current statistical methods for microarray-based comparative genomic hybridization (array-CGH) analysis generally assume certain relationships among adjacent markers on the same chromosome, and these assumptions may be questionable. For an SNP-array-based CGH study, multiple normal reference SNP arrays were collected. In order to utilize these normal reference SNP arrays, we derived an empirical distribution of signal ratios for each SNP marker. With an assumed threshold value for the overall error rate control and the defined signal ratio ranges for chromosomal amplification and deletion, we proposed a procedure to identify chromosomal alteration regions based on several bootstrapped one-sample t-tests and the false discovery rate control. When we have multiple arrays for different individuals with the same disease, our method can also be used to detect SNP markers for chromosomal alteration regions that are common among these individuals. We applied our method to a published SNP array data set for breast carcinoma cell lines. For an individual with breast cancer, numerous chromosomal alteration regions were identified. Compared to results of previous studies, our method identified more chromosomal alteration regions, with some being implicated in the literature to harbor genes associated with breast cancer. For multiple cancer arrays, our results suggested the existence of common chromosomal alteration regions. However, a high proportion of false positives also indicated that genetic variations among different individuals with breast cancer can be present.
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PMID:A statistical method to detect chromosomal regions with DNA copy number alterations using SNP-array-based CGH data. 1568 May 85

Gene amplification, an important mechanism of oncogene activation in breast cancer, can have both prognostic and therapeutic implications. In this work, an attempt is made to identify amplified genes that can be used to improve prognostication in breast cancer. A series of 52 node-negative tumours was screened for genomic gains at 57 loci by array-CGH. A subset of these genes was identified that could divide the series into two divergent outcome groups of either long-term survivors or early disease-related deaths (p = 0.01) using a combination of k-means clustering and statistical analysis. The prognostic significance of amplification of four of the genes (EMS1, TOP2A, CCNE1, and ERBB2) was then evaluated, using fluorescent in situ hybridization on a tissue microarray, in a second larger 'validation' series of 232 tumours with a median follow-up of 4.8 years. Adverse disease-related outcome was associated with amplification of TOP2A (p = 0.004); ERBB2 (p = 0.002); and with the combined amplification of TOP2A, ERBB2, and EMS1 (p = 0.01). EMS1 amplification was more common (26% of cases) than previously reported but, in isolation, had no prognostic significance. Amplification of CCNE1, seen in only 6% of cases, had no prognostic role. These results indicate that the complementary use of array-CGH and tissue microarrays has the potential to help in the identification and validation of molecular markers that can be used to classify breast cancers into different prognostic groups.
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PMID:Identification and validation of prognostic markers in breast cancer with the complementary use of array-CGH and tissue microarrays. 1568 39

Genomic imbalances in 31 formalin-fixed and paraffin-embedded primary tumors of advanced breast cancer were analyzed by microarray-based comparative genomic hybridization (matrix-CGH). A DNA chip was designed comprising 422 mapped genomic sequences including 47 proto-oncogenes, 15 tumor suppressor genes, as well as frequently imbalanced chromosomal regions. Analysis of the data was challenging due to the impaired quality of DNA prepared from paraffin-embedded samples. Nevertheless, using a method for the statistical evaluation of the balanced state for each individual experiment, we were able to reveal imbalances with high significance, which were in good concordance with previous data collected by chromosomal CGH from the same patients. Owing to the improved resolution of matrix-CGH, genomic imbalances could be narrowed down to the level of individual bacterial artificial chromosome and P1-derived artificial chromosome clones. On average 37 gains and 13 losses per tumor cell genome were scored. Gains in more than 30% of the cases were found on 1p, 1q, 6p, 7p, 8q, 9q, 11q, 12q, 17p, 17q, 20q, and 22q, and losses on 6q, 9p, 11q, and 17p. Of the 51 chromosomal regions found amplified by matrix-CGH, only 12 had been identified by chromosomal CGH. Within these 51 amplicons, genome database information defined 112 candidate genes, 44 of which were validated by either PCR amplification of sequence tag sites or DNA sequence analysis.
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PMID:Candidate genes in breast cancer revealed by microarray-based comparative genomic hybridization of archived tissue. 1569 85

Loss of genetic material from chromosome arm 8p occurs frequently in human breast carcinomas, consistent with this region of the genome harboring one or more tumor suppressor genes (TSGs). We used the complementary techniques of microsatellite-based LOH, high-density FISH, and conventional CGH on 6 breast cancer cell lines (MCF7, SKBR3, T47D, MDA MB453, BT549, and BT474) to investigate the molecular cytogenetic changes occurring on chromosome 8 during tumorigenesis, with particular emphasis on 6 potential TSGs on 8p. We identified multiple alterations of chromosome 8, including partial or complete deletion of 8p or 8q, duplication of 8q, and isochromosome 8q. The detailed FISH analysis showed several complex rearrangements of 8p with differing breakpoints of varying proximity to the genes of interest. High rates of LOH were observed at markers adjacent to or within PCM1, DUSP4/MKP2, NKX3A, and DLC1, supporting their status as candidate TSGs. Due to the complex ploidy status of these cell lines, relative loss of 8p material detected by CGH did not always correlate with microsatellite-based LOH results. These results extend our understanding of the mechanisms accompanying the dysregulation of candidate tumor suppressor loci on chromosome arm 8p, and identify appropriate cellular systems for further investigation of their biological properties.
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PMID:Complex CGH alterations on chromosome arm 8p at candidate tumor suppressor gene loci in breast cancer cell lines. 1599 69

Breast cancer is the most common malignant disease in Caucasian women, but is less frequent in Chinese women. The molecular basis for such ethnical difference in disease pathogenesis remains unknown. To address this issue, we performed allelotyping analysis of formalin-fixed, paraffin-embedded samples from 21 Chinese patients with breast cancer using 59 fluorescently tagged oligonucleotide primers amplifying microsatellite loci. Loss of heterozygosity (LOH) was found in all tumor samples. Frequent allelic losses were identified at markers D3S1578 (56%); D7S507 (55%); D1S2766 (50%); D17S789 and D17S946 (43% each); D19S814 (35%); D2S162, D13S158 and D13S296 (33% each); D1S551 and D1S2800 (29% each); D3S1597 and D6S260 (22% each); and D1S1588 (21%). To compare our data to previous reports, we determined the band-specific frequency of chromosomal imbalances in breast cancer karyotypes reported in the Mitelman database, and from the CGH results of cases accessible through the Progenetix website. Furthermore, published LOH analyses of breast cancer cases were compared to our own LOH results, demonstrating the most common chromosomal regions affected by allelic losses. The combined results provide a comprehensive view of genetic losses in breast cancers, indicating the comparability of these different techniques and suggesting the presence of a distinct subset of breast cancers with high-frequency LOH at chromosomes 1 and 2p in Chinese patients.
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PMID:Genetic losses in breast cancer: toward an integrated molecular cytogenetic map. 1599 70


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