PubMed Health⌕ Search

Biomedical subjects

S Solinas-Toldo

Publications and source records attributed to S Solinas-Toldo.

At least 19 recordsLinked to original sources
PubMed2000

Adrenocortical carcinoma is characterized by a high frequency of chromosomal gains and high-level amplifications.

Distinction of adrenocortical carcinoma from benign adrenocortical lesions by standard criteria is often difficult. In order to search for additional diagnostic parameters, a series of 25 adrenocortical tumors, 8 adenomas, 14 primary carcinomas, 1 metastasis, and the 2 adrenocortical carcinoma cell lines SW13 and NCI-H295 were analyzed by the approach of comparative genomic hybridization (CGH). Except for the two smallest adenomas, all tumors showed chromosomal imbalances with a high incidence of chromosomal gains, most frequently involving chromosomes or chromosome arms 5, 7, 8, 9q, 11q, 12q, 14q, 16, 17q, 19, 20, and 22q. The only significant loss of material concerned the distal part of 9p. Furthermore, 21 high-level amplifications were identified in 15 different regions of the genome. The consensus regions of recurrent gains and the focal high-level amplifications allowed identification of a series of chromosomal subregions containing candidate proto-oncogenes of potential pathogenic function in adrenocortical tumors: 1p34.3-pter, 1q22-q25, 3p24-pter, 3q29, 7p11.2-p14, 9q34, 11q12-11q13, 12q13, 12q24.3, 13q34, 14q11.2-q12, 14q32, 16p, 17q24-q25, 19p13.3, 19q13.4, and 22q11.2-q12. A subset of the CGH data was independently confirmed by interphase cytogenetics. Interestingly, the adenomas larger than 4 cm contained gained material of regions also overrepresented in carcinomas. In addition, several chromosomal gains, in particular the high-level amplifications, were exclusive for the malignant status of the tumors. These data indicate that the larger adrenal lesions need to be carefully considered in the diagnosis of adrenocortical tumors, and that genetic aberrations might provide useful markers for a better diagnostic differentiation.

Adolescent↗
PubMed1999

Strategies for the detection of disease genes in pancreatic cancer.

The present review summarizes our strategies aimed at identifying and characterizing genetic alterations occurring at the transcriptional and chromosomal level in pancreatic cancer. To study transcriptional alterations we have used a number of techniques including modified versions of differential hybridizations and cDNA RDA (representational difference analysis). These approaches have led to the identification of more than 500 genes with differential expression in pancreatic cancer. To study chromosomal aberrations occurring in pancreatic cancer tissues we used comparative genomic hybridization (CGH). This allowed the identification of a number of chromosomal regions containing putative tumor suppressor genes or oncogenes. Genes isolated in both approaches represent potential new disease genes for pancreatic cancer and are at present being characterized by individual or serial analysis.

Amino Acid Sequence↗
PubMed1999

Novel technology for detection of genomic and transcriptional alterations in pancreatic cancer.

AIM: The present review summarizes our strategies aimed at identifying and characterizing genetic alterations occurring at the transcriptional and chromosomal level in pancreatic cancer. METHODS: To study transcriptional alterations we have used a number of techniques including modified versions of differential hybridizations and cDNA-RDA (representational difference analysis). Comparative genomic hybridization (CGH) was used to study chromosomal aberrations occurring in pancreatic cancer tissues. RESULTS: The study of transcriptional alterations led to the identification of more than 500 genes with differential expression in pancreatic cancer. The sum of these alterations represented the first expression profile characteristic for pancreatic tumors. The CGH analysis allowed the identification of a number of chromosomal regions containing putative tumor suppressor genes or oncogenes. These regions are presently being characterized at the molecular level. In a first approach the myb-oncogene was identified as the relevant oncogene of an amplification on 6q occurring in up to 10% of pancreatic cancer patients. CONCLUSIONS: Genes isolated in both approaches represent potential new disease genes for pancreatic cancer and are at present being characterized by individual or serial analysis.

Chromosome Aberrations↗
PubMed1998

Mapping of chromosomal imbalances in gastric adenocarcinoma revealed amplified protooncogenes MYCN, MET, WNT2, and ERBB2.

Gastric adenocarcinoma is a malignant tumor with a high incidence and a low survival rate. In order to identify genetic alterations associated with this tumor, we screened 23 gastric adenocarcinomas for recurrent chromosomal imbalances by using comparative genomic hybridization (CGH). The most common gains of chromosomal material were found on chromosome arms 20q (10 cases), 16p (7 cases), and 1q (4 cases) and on chromosome 11 (4 cases). Losses were observed on chromosome arms 4q, 5q, 9p, and 21q (3 cases each). Four tumors exhibited high-level amplifications localized on chromosome regions 2p23-p24, 7q31-q32, 8p21-p22, 10q25-q26, 11q13, 17q11-q21, and 20q. Based on the position of these amplifications, candidate (onco)genes were selected and subsequently tested by Southern blot analysis of the respective tumors. Of the seven tested candidates, MYCN, MET, WNT2, and ERBB2 were found to participate in the amplicons of the respective tumor samples. Of these four presumably activated oncogenes, two, MYCN and WNT2, were previously not assumed to play a pathogenic role in stomach cancer. Among the other regions of imbalance, gain of 20q seems particularly interesting, because it is found in almost half of the analyzed cases and is highly amplified. Our data allowed us to narrow the relevant region down to the commonly gained bands 20q12-q13.1. This and other imbalanced regions provide a basis for searching new putative oncogenes and tumor suppressor genes involved in the development or progression of gastric adenocarcinoma.

Adenocarcinoma↗
PubMed1997

Characterization of a high copy number amplification at 6q24 in pancreatic cancer identifies c-myb as a candidate oncogene.

In a recent study designed to identify chromosomal aberrations in pancreatic cancer tissues using comparative genomic hybridization, a high copy number amplification on 6q was detected. To identify the most likely candidate oncogene, the extension of the amplification in pancreatic cancer tissues and cell lines was determined by Southern blot analysis. Exon trapping was performed with DNA from a yeast artificial chromosome clone containing the complete minimally amplified region. Only fragments from two genes, namely, the c-myb oncogene and a novel gene, were shown to be amplified. The c-myb proto-oncogene was amplified in 10% of the pancreatic carcinoma tissues and in the pancreatic cancer cell line PC2. Interestingly, the c-myb oncogene was overexpressed not only in the amplified samples but also in the majority of the examined pancreatic cancer tissues and cell lines, suggesting that amplification is only one of the mechanisms leading to overexpression. In contrast, the novel gene, which was called human eRF3b (eukaryotic release factor 3b), seems to be only coamplified with c-myb. Genetic alterations of c-myb were mainly found in advanced tumors, indicating a possible correlation to tumor progression and aggressive tumor phenotypes.

Adenocarcinoma↗
PubMed1997

Specific chromosomal imbalances in human papillomavirus-transfected cells during progression toward immortality.

High risk human papillomaviruses (HPVs) known to be closely associated with cervical cancer, such as HPV16 and HPV18, have the potential to immortalize human epithelial cells in culture. Four lines of HPV-transfected keratinocytes were analyzed by comparative genomic hybridization at different time points after transfection. A number of chromosomal imbalances was found to be highly characteristic for the cultures progressing toward immortality. Whereas several of these were new and previously not found as recurrent aberrations in cervical tumors, some were identical to chromosomal changes observed during cervical carcinogenesis. The data put new emphasis on the studied cell system as a relevant model for HPV-induced pathogenesis.

Cell Line↗
PubMed1997

Chromosomal localization of six bovine microsatellite markers.

Six lambda genomic clones containing polymorphic microsatellite (MS) markers were assigned to bovine chromosomes 1, 3, 5, 7, 13 and 24 by fluorescence in situ hybridization (FISH). Linkage data for four MS markers were presented earlier and linkage data for the remaining two on chromosome 7 and 24 are presented here. All assignments either orient or confirm the orientation of linkage groups relative to the centromere. A comparison of physical assignments and linkage intervals was possible on chromosome 5 (three loci, 38 cM) and 13 (two loci, 6 cM).

Animals↗
PubMed1997

Matrix-based comparative genomic hybridization: biochips to screen for genomic imbalances.

Comparative genomic hybridization (CGH) to metaphase chromosomes has been widely used for the genome-wide screening of genomic imbalances in tumor cells. Substitution of the chromosome targets by a matrix consisting of an ordered set of defined nucleic acid target sequences would greatly enhance the resolution and simplify the analysis procedure, both of which are prerequisites for a broad application of CGH as a diagnostic tool. However, hybridization of whole genomic human DNA to immobilized single-copy DNA fragments with complexities below the megabase pair level has been hampered by the low probability of specific binding because of the high probe complexity. We developed a protocol that allows CGH to chips consisting of glass slides with immobilized target DNAs arrayed in small spots. High-copy-number amplifications contained in tumor cells were rapidly scored by use of target DNAs as small as a cosmid. Low-copy-number gains and losses were identified reliably by their ratios by use of chromosome-specific DNA libraries or genomic fragments as small as 75 kb cloned in PI or PAC vectors as targets, thus greatly improving the resolution achievable by chromosomal CGH. The ratios obtained for the same chromosomal imbalance by matrix CGH and by chromosomal CGH corresponded very well. The new matrix CGH protocol provides a basis for the development of automated diagnostic procedures with biochips designed to meet clinical needs.

Chromosome Aberrations↗
PubMed1996

Mapping of chromosomal imbalances in pancreatic carcinoma by comparative genomic hybridization.

To identify recurrent chromosomal imbalances in pancreatic adenocarcinoma, 27 tumors were analyzed by using comparative genomic hybridization. In 23 cases chromosomal imbalances were found. Gains of chromosomal material were much more frequent than losses. The most common overrepresentations were observed on chromosomes 16p (eight cases), 20q (seven cases), 22q (six cases), and 17q (five cases) and under-representations on a subregion of chromosome 9p (eight cases). Distinct high-level amplifications were found on 1p32-p34, 6q24, 7q22, 12p13, and 22q. These data provide evidence for a number of new cytogenetically defined recurrent aberrations which are characteristic of pancreatic carcinoma. The overrepresented or underrepresented chromosomal regions represent candidate regions for potential oncogenes and tumor suppressor genes, respectively, possibly involved in pancreatic tumorigenesis.

Adenocarcinoma↗
PubMed1996

Cloning and chromosomal mapping of bovine interleukin-2 receptor gamma gene.

Interleukin-2 receptor (IL-2R) gamma chain, a member of the cytokine receptor superfamily, forms a high-affinity receptor with IL-2R alpha and beta chains that plays an important role in interleukin-2 (IL-2) signal transduction. We have cloned and characterized the bovine IL-2Rgamma gene and corresponding cDNA. Bovine IL-2Rgamma is a single-copy gene that contains 8 exons and spans approximately 3.8 kb. The promoter region lacks conventional TATA and CCAAT consensus sites, but contains several regulatory elements that are recognition sites for the GATA binding proteins, AP-1 and AP-2. Physical assignment by fluorescence in situ hybridization (FISH) placed the bovine IL-2Rgamma gene on chromosome Xq23.

Amino Acid Sequence↗
PubMed1996

Efficacy of current molecular cytogenetic protocols for the diagnosis of chromosome aberrations in tumor specimens.

Molecular cytogenetics provides a powerful link between molecular genetic analysis and chromosome morphology, allowing one to pinpoint structurally aberrant chromosome regions on the molecular level. Fluorescence in situ hybridization with selected DNA probes allows the design of efficient and sensitive tools for the diagnosis of chromosomal aberrations present in tumor cells. Comparative genomic hybridization (CGH) allows the identification of chromosomal imbalances in a comprehensive manner, and is applied to solid tumors and hematological malignancies in order to (i) identify clonal differences within a specimen, (ii) contribute to tumor classifications, (iii) identify recurrent chromosomal gains and losses as starting points for the characterization and isolation of pathogenetically relevant genes, such as proto-oncogenes and tumor suppressor genes respectively, (iv) identify imbalances of prognostic relevance, (v) detect high-copy-number amplification and other markers of genetic instability, and (vi) analyze chromosomal imbalances during tumor progression.

Chromosome Aberrations↗
PubMed1995

Comparative genome map of human and cattle.

Chromosomal homologies between individual human chromosomes and the bovine karyotype have been established by using a new approach termed Zoo-FISH. Labeled DNA libraries from flow-sorted human chromosomes were used as probes for fluorescence in situ hybridization on cattle chromosomes. All human DNA libraries, except the Y chromosome library, hybridized to one or more cattle chromosomes, identifying and delineating 50 segments of homology, most of them corresponding to the regions of homology as identified by the previous mapping of individual conserved loci. However, Zoo-FISH refines the comparative maps constructed by molecular gene mapping of individual loci by providing information on the boundaries of conserved regions in the absence of obvious cytogenetic homologies of human and bovine chromosomes. It allows study of karyotypic evolution and opens new avenues for genomic analysis by facilitating the extrapolation of results from the human genome initiative.

Animals↗
PubMed1995

The bovine interleukin-4 gene: genomic organization, localization, and evolution.

Interleukin-4 (IL4) is involved in the immune response to certain parasites and possibly in the development of some atopic diseases since it triggers the T helper 2 lymphocyte response. Therefore, IL4 is a candidate gene, for example, for disease association studies and gene mapping. We isolated bovine IL4 cosmids and determined the genomic organization. Fragments carrying the exons as well as 725 base pairs (bp) from the 5' flanking and 190 bp from the 3' flanking region were cloned and sequenced. The first 481 base pairs of the 5' flanking region, including the putative promoter sequences, are surprisingly similar (92%) between cattle and human. In addition, we cloned and sequenced a mixed [(t/g)a]m(ca)n repeat located approximately 35 kilobases upstream from the IL4 gene. It showed seven repeat length alleles in a limited number of animals. The IL4 gene has been assigned to 7q15-q21 by fluorescence in situ hybridization in cattle. Evolutionary aspects are discussed on the basis of sequence data as well as interspecies chromosomal homologies.

Amino Acid Sequence↗
PubMed1995

Combined Q-banding and fluorescence in situ hybridization for the identification of bovine chromosomes 1 to 7.

Eleven probes were assigned to bovine chromosomes 1 to 7 by fluorescence in situ hybridization (FISH). The identification of chromosomes was based on QFQ-banding prior to in situ hybridization and comparison with the Reading Conference (1976) and ISCNDA (1989) standards. The probes used for FISH can now be utilized as identification and discrimination features for bovine chromosomes 1 to 7 and particularly for chromosomes 4 and 6, which are difficult to distinguish. Comparison of our mapping data with previous assignments and of the standard chromosome banding patterns prompt us to propose a change in the ISCNDA nomenclature: ISCNDA chromosome 4 should be named chromosome 6 and vice versa. Chromosome 4 is marked by the ribosomal RNA cluster RNR3, and chromosome 6 is characterized by the casein gene cluster and an anonymous satellite (D6Z1).

Animals↗