Comparative Genomic Hybridization Reveals Complex Genetic Changes in Primary Breast Cancer Tumors and Their Cell Lines

Larramendy, Marcelo L.; Lushnikova, Tamara; Björkqvist, Anna‐Maria; Wistuba, Ignacio I.; Virmani, Arvind K.; Shivapurkar, Narayan; Gazdar, Adi F.; Knuutila, Sakari

doi:10.1016/s0165-4608(99)00226-5

Cited by 72 publications

(63 citation statements)

References 18 publications

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“…This was in full agreement with previous chromosomal CGH results by us and other groups (Courjal and Theillet, 1997;Tirkkonen et al, 1998;Malamou-Mitsi et al, 1999;Larramendy et al, 2000). Interestingly, gains at 1q were of low-to-moderate level with a lower prevalence of amplifications compared to other chromosomes.…”

Section: Discussionsupporting

confidence: 92%

“…Fifty to 60% of breast tumours analysed by CGH presented gains at 1q, whereas the short arm showed predominantly losses, except the 1p31 -p32 region which presented occasional gains (Courjal and Theillet, 1997;Tirkkonen et al, 1998). Gains at 1q frequently affect the whole arm; however, a number of tumours or cell lines exhibit interstitial gains sometimes reduced to a chromosomal band or sub-band (Courjal and Theillet, 1997;Larramendy et al, 2000). These data suggesting the existence at 1q of several regions of gains were thus concordant with LOH studies, indicating the occurrence of at least four regions of allelic imbalance in breast tumours (Kerangueven et al, 1997).…”

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confidence: 99%

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Genetic profiling of chromosome 1 in breast cancer: mapping of regions of gains and losses and identification of candidate genes on 1q

et al. 2006

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Chromosome 1 is involved in quantitative anomalies in 50 -60% of breast tumours. However, the structure of these anomalies and the identity of the affected genes remain to be determined. To characterise these anomalies and define their consequences on gene expression, we undertook a study combining array-CGH analysis and expression profiling using specialised arrays. Array-CGH data showed that 1p was predominantly involved in losses and 1q almost exclusively in gains. Noticeably, high magnitude amplification was infrequent. In an attempt to fine map regions of copy number changes, we defined 19 shortest regions of overlap (SROs) for gains (one at 1p and 18 at 1q) and of 20 SROs for losses (all at 1p). These SROs, whose sizes ranged from 170 kb to 3.2 Mb, represented the smallest genomic intervals possible based on the resolution of our array. The elevated incidence of gains at 1q, added to the wellestablished concordance between DNA copy increase and augmented RNA expression, made us focus on gene expression changes at this chromosomal arm. To identify candidate oncogenes, we studied the RNA expression profiles of 307 genes located at 1q using a home-made built cDNA array. We identified 30 candidate genes showing significant overexpression correlated to copy number increase. In order to substantiate their involvement, RNA expression levels of these candidate genes were measured by quantitative (Q)-RT -PCR in a panel of 25 breast cancer cell lines previously typed by array-CGH. Q -PCR showed that 11 genes were significantly overexpressed in the presence of a genomic gain in these cell lines, and 20 overexpressed when compared to normal breast.

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Section: Discussionsupporting

confidence: 92%

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confidence: 99%

Genetic profiling of chromosome 1 in breast cancer: mapping of regions of gains and losses and identification of candidate genes on 1q

et al. 2006

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“…In all, novel sequences were detected. Interestingly, some of these regions (1q41, 7p22, 8p11.23, 8q13.1, 8q22.3, 10q21.3, 10q24.32, 19q13.1, 20p11.23) have been described as amplified sequences in other human malignancies (Bruch et al, 1998;Curtis et al, 1998;Du Plessis et al, 1999;Larramendy et al, 2000;Pimkhaokham et al, 2000;Tang et al, 2002;Dai et al, 2003;Lukasova et al, 2004;Rao et al, 2004). The RLGS data does not allow us to discriminate between DNA copy number gains that have integrated at the location of the original sequence or extra DNA localized in extrachromosomal double minutes.…”

Section: Resultsmentioning

confidence: 99%

DNA copy number gains in head and neck squamous cell carcinoma

et al. 2005

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Gene amplification, a common mechanism for oncogene activation in cancer, has been used as a tag for the identification of novel oncogenes. DNA amplification is frequently observed in head and neck squamous cell carcinoma (HNSCC) and potential oncogenes have already been reported. We applied restriction landmark genome scanning (RLGS) to study gene amplifications and low-level copy number changes in HNSCC in order to locate previously uncharacterized regions with copy number gains in primary tumor samples. A total of 63 enhanced RLGS fragments, indicative of DNA copy number changes, including gains of single alleles, were scored. Enhanced sequences were identified from 33 different chromosomal regions including those previously reported (e.g. 3q26.3 and 11q13.3) as well as novel regions (e.g. 3q29, 8q13.1, 8q22.3, 9q32, 10q24.32, 14q32.32, 17q25.1 and 20q13.33). Furthermore, our data suggest that amplicons 11q13.3 and 3q26.3-q29 may be divided into possibly two and three independent amplicons, respectively, an observation supported by published microarray expression data.

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“…[25][26][27][28][29] In addition, amplification of 20q12-13 has been demonstrated specifically in breast and ovarian carcinomas. 30,31 Recent interest in HE4 has been generated by the consistent demonstration of overexpression in ovarian carcinomas in comparison to normal ovarian tissue. Although a meta-analysis of gene expression profiles of ovarian carcinomas found HE4 to be the most frequently upregulated gene, 32 a large scale evaluation of HE4 gene and protein expression in both normal tissues and common nonovarian carcinomas has not been performed thus far.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of HE4 expression in normal and malignant human tissues

2006

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The HE4 (WFDC2) gene encodes a WAP-type four disulphide core domain-containing protein with a presumptive role in natural immunity. Multiple studies have consistently identified upregulation of HE4 gene expression in carcinomas of the ovary; however, the expression in normal and malignant adult tissues has not been examined in detail. Here, we examined the expression of the HE4 gene and protein in a large series of normal and malignant adult tissues by oligonucleotide microarray and tissue microarray, respectively. HE4 gene expression was highest in normal human trachea and salivary gland, and to a lesser extent, lung, prostate, pituitary gland, thyroid, and kidney. In a series of 175 human adult tumors, gene expression was highest in ovarian serous carcinomas. However, adenocarcinomas of the lung, and occasional breast, transitional cell and pancreatic carcinomas had moderate or high levels of HE4 expression. Using tissue microarrays and full tissue sections of normal and 448 neoplastic tissues, HE4 immunoreactivity was found in normal glandular epithelium of the female genital tract and breast, the epididymis and vas deferens, respiratory epithelium, distal renal tubules, colonic mucosa, and salivary glands, consistent with HE4 gene expression. In addition to consistent positivity in ovarian carcinoma, some pulmonary, endometrial, and breast adenocarcinomas, mesotheliomas, and less often, gastrointestinal, renal and transitional cell carcinomas were also positive. Knowledge of the expression patterns of HE4 in our survey is useful for application in histopathologic diagnosis, and should be taken into consideration in future studies that examine the role of HE4 as a serological tumor biomarker or as a target for gene-based therapy.

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Comparative Genomic Hybridization Reveals Complex Genetic Changes in Primary Breast Cancer Tumors and Their Cell Lines

Cited by 72 publications

References 18 publications

Genetic profiling of chromosome 1 in breast cancer: mapping of regions of gains and losses and identification of candidate genes on 1q

Genetic profiling of chromosome 1 in breast cancer: mapping of regions of gains and losses and identification of candidate genes on 1q

DNA copy number gains in head and neck squamous cell carcinoma

Comprehensive analysis of HE4 expression in normal and malignant human tissues

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