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- Adeyinka, Adewale, et al.
(author)
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Comparative cytogenetic and DNA flow cytometric analysis of 242 primary breast carcinomas
- 2003
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In: Cancer Genetics and Cytogenetics. - 0165-4608. ; 147:1, s. 62-67
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Journal article (peer-reviewed)abstract
- The cytogenetic and DNA flow cytometric findings in 242 breast carcinomas were compared. The combined use of both techniques improved the detection of abnormal cell populations from 65% by cytogenetic analysis alone and 59% by DNA flow cytometric analysis alone to 84%. Informative and comparable cytogenetic and flow cytometric data were obtained for 155 tumors. Among these 155 tumors, there was good concordance (64%) between the estimates of genomic changes by the two methods. Most discrepancies were among the DNA-diploid cases, where cytogenetic analysis detected small genomic changes. There were, however, also some exceptions in which large genomic changes detected by one method were missed by the other. Of the specific breast cancer-associated cytogenetic aberrations subjected to separate correlation analysis, polysomy for chromosome 20 was significantly associated with a high S-phase fraction, whereas loss of the long arm of chromosome 16 and/or the presence of a der(1;16) were significantly associated with a low S-phase fraction. Our data show that cytogenetic and DNA flow cytometric analyses of breast carcinomas give largely comparable results, and that combining data from both methods significantly improves the information obtained by either technique used alone on the genetic abnormalities in these tumors.
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| 2. |
- Adeyinka, Adewale
(author)
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Cytogenetic studies of primary and metastatic breast cancer
- 1999
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Doctoral thesis (other academic/artistic)abstract
- A series of primary and metastatic breast carcinomas obtained from female and male patients were cytogenetically analysed. Trisomy 12 was identified as a recurrent and sometimes early event in breast carcinogenesis. Also, multiple polysomies involving chromosomes 1, 5, 6, 7, 12, 16, 18, and 19 were identified as a possible pathway of progression in a subset of carcinomas. Among the male breast carcinomas, +7, del(16)(q13) and +20 were identified as recurrent changes. A study of invasive breast carcinomas of histological types usually considered to be prognostically favourable revealed that medullary carcinomas are cytogenetically more complex than mucinous and tubular carcinomas, with medullary carcinomas often exhibiting karyotypic features that have previously been associated with aggressive breast carcinomas, i.e., highly complex chromosome aberrations with near-triploid chromosome numbers. A cytogenetic comparison of primary breast carcinomas and their lymph node metastases, as well as a comparison of chromosomal imbalances in node-positive and node-negative primary breast carcinomas, showed that monosomy for chromosomes 17, 18, and 22 seem to be important in the metastatic process. On the other hand, loss of material from the proximal part of the long arm of chromosome 6 and loss of the long arm of chromosome 16 were preferentially associated with a node-negative phenotype in primary breast cancer.
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| 3. |
- Johannsson, Oskar T, et al.
(author)
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Characterization of a novel breast carcinoma xenograft and cell line derived from a BRCA1 germ-line mutation carrier
- 2003
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In: Laboratory Investigation. - 1530-0307. ; 83:3, s. 96-387
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Journal article (peer-reviewed)abstract
- A human tumor xenograft (L56Br-X1) was established from a breast cancer axillary lymph node metastasis of a 53-year-old woman with a BRCA1 germ-line nonsense mutation (1806C>T; Q563X), and a cell line (L56Br-C1) was subsequently derived from the xenograft. The xenograft carries only the mutant BRCA1 allele and expresses mutant BRCA1 mRNA but no BRCA1 protein as determined by immunoprecipitation or Western blotting. The primary tumor, lymph node metastasis, and xenograft were hypodiploid by DNA flow cytometry, whereas the cell line displayed an aneuploidy apparently developed via polyploidization. Cytogenetic analysis, spectral karyotyping, and comparative genomic hybridization of the cell line revealed a highly complex karyotype with numerous unbalanced translocations. The xenograft and cell line had retained a somatic TP53 missense mutation (S215I) originating from the primary tumors, as well as a lack of immunohistochemically detectable expression of steroid hormone receptors, epidermal growth factor receptor, human epidermal growth factor receptor 2 (HER-2), and keratin 8. Global gene expression analysis by cDNA microarrays supported a correlation between the expression profiles of the primary tumor, lymph node metastasis, xenograft, and cell line. We conclude that L56Br-X1 and L56Br-C1 are useful model systems for studies of the pathogenesis and new therapeutic modalities of BRCA1-induced human breast cancer.
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