bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of the wilms' tumor gene WT1 in human malignant mesothelioma cell lines and relationship to platelet‐derived growth factor A and insulin‐like growth factor 2 expression
Authors: Langerak Anthonie W. , Williamson Kathleen A. , Miyagawa Kiyoshi , Hagemeijer Anne , Versnel Marjan A. , Hastie Nicholas D. 
Published: February 2007

AbstractMutations in the WT1 tumor suppressor gene are known to contribute to the development of Wilms' tumor (WT) and associated gonadal abnormalities. WT1 is expressed principally in the fetal kidney, developing gonads, and spleen and also in the mesothelium, which lines the coelomic cavities. These tissues develop from mesenchymal components that have subsequently become epithelialized, and it has therefore been proposed that WT1 may play a role in this transition of cell types. To test the possible involvement of this gene in malignant mesothelioma, we have first studied its expression in a panel of human normal and malignant mesothelial cell lines. WT1 mRNA expression levels varied greatly between the cell lines and no specific chromosomal aberration on 11p, which could be related to the variation in WT1 expression in these cell lines, was observed. Furthermore, no gross deletions, rearrangements, or functionally inactivating point mutations in the WT1 coding region were identified. All four WT1 splice variants were observed at similar levels in these cell lines. The WT1 gene encodes a zinc‐finger transcription factor and the four protein isoforms are each believed to act as transcriptional repressors of certain growth factor genes. Lack of WT1 expression is thus predicted to result in growth stimulation of tumor cells. Binding of one particular WT1 isoform construct to the insulin‐like growth factor 2 (IGF2) and platelet‐derived growth factor A (PDGFA) gene promoters has been demonstrated to result in repression of these genes in transient transfection studies. Analysis of IGF2 and PDGFA mRNA expression levels compared with WT1 mRNA expression levels failed to demonstrate an inverse correlation in the mesothelial cell lines, which endogenously express these genes. Finally, the putative role of WT1 in the transition of cell types was investigated. No obvious correlation between WT1 expression levels and cell morphology of the malignant mesothelial cell lines was evident from this study. Moreover, no change in WT1 expression was observed in normal mesothelial cells which were, by alteration of culture conditions, manipulated to switch from the mesenchymal to epithelial morphology.
N‐ and KRAS mutations in primary testicular germ cell tumors: Incidence and possible biological implications
Authors: Olie Robert A. , Looijenga Leendert H. J. , Boerrigter Lucie , Top Bert , Rodenhuis Sjoerd , Langeveld An , Mulder Maarten P. , Oosterhuis J. Wolter 
Published: February 2007

AbstractRecently, conflicting results have been reported on the incidence of RAS mutations in primary testicular germ cell tumors of adults (TGCTs). In four studies a low incidence of mutations (less than 15%) in a variety of TGCTs or derived cell lines was found, whereas in two other studies a high incidence of N‐ or KRAS mutations (over 40%) was shown. A total of 62 testicular seminomas (SE) and 34 nonseminomatous TGCTs (NS) were studied thus far. The largest series consisted of 42 TGCTs, studied on paraffin embedded tissue. We present the results of analysis for the presence of N‐ and KRAS mutations, in codons 12, 13, and 61, in snap frozen samples of 100 primary TGCTs, comprising 40 SE and 60 NS. Using the polymerase chain reaction (PCR) and allele specific oligonucleotide hybridization (ASO), mutations were found in five SE (three in NRAS and two in KRAS, all codon 12), and in one NS (KRAS, codon 12). To exclude underestimation of the incidence of RAS mutations in TGCTs due to the presence of an excess of wild type alleles in the analyzed sample, a PCR technique preferentially amplifying KRAS alleles with a mutation in codon 12 was applied to all SE. This approach, allowing a 250 times more sensitive assay, resulted in the detection of only one additional SE with a mutation. Based on a critical analysis of published data and on our results from the largest series of frozen samples investigated thus far, we conclude that N‐ or KRAS mutations are rare and apparently not essential for initiation or progression of TGCTs.
Screening for germ‐line mutations in the NF2 Gene
Authors: Mérel Philippe , Hoang‐Xuan Khé , Sanson Marc , Bijlsma Emilia , Rouleau Guy , Laurent‐Puig Pierre , Pulst Stephan , Baser Michael , Lenoir Gilbert , Sterkers Jean Marc , Philippon Jacques , Resche François , Mautner Victor F. , Fischer Georges , Hulsebos Theo , Aurias Alain , Delattre Olivier , Thomas Gilles 
Published: February 2007

AbstractNeurofibromatosis type 2 (NF2) is a monogenic dominantly inherited disease that predisposes to the development of tumors of the nervous system, particularly meningiomas and schwannomas. The gene which, when altered, causes NF2, is localized on chromosome 22 and has recently been identified. The NF2 gene is also the site of somatic mutation in tumors, suggesting that it might have a tumor suppressor activity. We here report a screening method for the detection of point mutations in NF2 which takes advantage of denaturing gradient gel electrophoresis (DGGE). This method efficiently screens 95% of the coding sequence and 90% of intron/exon junctions. When applied to 91 unrelated NF2 patients, it enabled the identification of 32 germ‐line mutations. Since mutations are found in only one third of the patients, it is expected that mutations or deletions affecting the promoter and/or intronic regions of the NF2 gene occur frequently. The characterized mutations are preferentially located within the 5° half of the gene. Most of them are predicted to lead to the synthesis of a truncated protein. A search for genotype/phenotype correlations showed that, at least in this series of patients, mild manifestations of the disease were associated with mutations which preserve the C‐terminal end of the protein.
A genetic model of melanoma tumorigenesis based on allelic losses
Authors: Walker Graeme J. , Palmer Jane M. , Walters Marilyn K. , Hayward Nicholas K. 
Published: February 2007

AbstractPrevious karyotypic studies have indicated a possible series of non‐random chromosomal events involved in progression of melanoma. We sought to verify and augment this model of melanocyte tumorigenesis by studying allelic deletions of markers mapping to these regions in 30 matched pairs of melanoma and constitutional DNA samples. Polymorphic loci on chromosomes 1, 7, 10, 11, 17, and 21 were analyzed and data combined with those previously obtained for chromosome arms 6q and 9p in the same series of tumours. The most frequent and earliest deletions were found on 9p (57%) and 10q (32%). With the exception of one case, no sample had loss of markers on another chromosome without concomitant loss of markers on 9p or 10q. Losses on 6q were also a frequent (31%) and early event whereas losses of loci on distal 1p (22%) or 11q (26%) occurred only in metastatic melanomas. A “background” rate (0–17%) of allele loss was seen on chromosomes 7, 17, and 21. These data strongly support the previous model based on karyotypic findings in melanocytic lesions. However, we have been able to further augment that model by delimiting the regions of loss on 10q, to that distal to D10S254, and on 1p, to between D1S243 and D1S160.
Chromosome analysis of 97 primary breast carcinomas: Identification of eight karyotypic subgroups
Authors: Pandis Nikos , Jin Yuesheng , Gorunova Ludmila , Petersson Catarina , Bardi Georgia , Idvall Ingrid , Johansson Bertil , Ingvar Christian , Mandahl Nils , Mitelman Felix , Heim Sverre 
Published: February 2007

AbstractChromosome banding analysis of 97 short‐term cultured primary breast carcinomas revealed clonal aberrations in 79 tumors, whereas 18 were karyotypically normal. In 34 of the 79 tumors with abnormalities, two to eight clones per case were detected; unrelated clones were present in 27 (34%) cases, whereas only related clones were found in seven. These findings indicate that a substantial proportion of breast carcinomas are of polyclonal origin. Altogether eight abnormalities were repeatedly identified both as sole chromosomal anomalies and as part of more complex karyotypes: the structural rearrangements i(1)(q10), der(1;16)(q10;p10), del(1)(q11–12), del(3)(p12–13p14–21), and del(6)(q21–22) and the numerical aberrations +7, +18, and +20. At least one of these changes was found in 41 (52%) of the karyotypically abnormal tumors. They identify a minimum number of cytogenetic subgroups in breast cancer and are likely to represent primary chromosome anomalies in this type of neoplasia. Other candidates for such a role are translocations of 3p12–13 and 4q21 with various partner chromosomes and inversions of chromosome 7, which also were seen repeatedly. Additional chromosomal aberrations that give the impression of occurring nonrandomly in breast carcinomas include structural rearrangements leading to partial monosomies for 1p, 8p, 11p, 11q, 15p, 17p, 19p, and 19q and losses of one copy of chromosomes X, 8, 9, 13, 14, 17, and 22. The latter changes were seen consistently only in complex karyotypes, however, and we therefore interpret them as being secondary anomalies acquired during clonal evolution.
Detection of the t(2;13)(q35;q14) and PAX3‐FKHR fusion in alveolar rhabdomyosarcoma by fluorescence in situ hybridization
Authors: Biegel Jaclyn A. , Nycum Lynn M. , Valentine Virginia , Barr Frederic G. , Shapiro David N. 
Published: February 2007

AbstractCytogenetic studies of the pediatric solid tumor alveolar rhabdomyosarcoma have demonstrated the presence of a consistent chromosomal translocation, t(2;13)(q35;q14). We recently identified PAX3 and FKHR as the genes on chromosomes 2 and 13, respectively, that are juxtaposed by this translocation. As one means of detecting the t(2;13) translocation in clinical specimens, we have developed a fluorescence in situ hybridization (FISH) assay that may be used for both interphase and metaphase cells. Translocation of the 5′ region of the FKHR gene to the derivative chromosome 2, and retention of the 3′ region of FKHR on the derivative chromosome 13 [(der(13)], were demonstrated in metaphase cells from a rhabdomyosarcoma cell line with a previously identified t(2;13) translocation. A 5′ PAX3 cosmid probe was shown to localize to 2q35 in normal cells, and to translocate to the der(13) in the rhabdomyosarcoma cell line. In order to detect the der(13) in interphase nuclei, we labeled the 3′FKHR and the 5′PAX3 cosmid probes with digoxigenin and biotin, respectively, and used these in a two‐color FISH assay. The presence of the der(13) was visualized as juxtaposed or overlapping red and green signals in metaphase and interphase tumor cells. The PAX3‐FKHR FISH assay was then applied to a series of cytogenetically characterized pediatric sarcoma cell lines. The presence of the der(13) was demonstrated by FISH in all cases containing a cytogenetically detectable t(2;13). The FISH assay was then applied to a series of 20 embryonal and alveolar rhabdomyosarcoma samples. All 10 of the alveolar rhabdomyosarcoma specimens demonstrated a der(13) with the FISH assay. We did not detect a PAX3‐FKHR fusion in 10 embryonal rhabdomyosarcoma cases. Thus, the two‐color FISH assay is a sensitive and rapid means of identifying the t(2;13) in rhabdomyosarcoma specimens, and it will be a useful adjunct for the diagnosis of pediatric small round cell tumors. The cosmid probes for the 5′ and 3′ regions of FKHR, as well as the probe for PAX3, will be useful for molecular cytogenetic studies of variant translocations in rhabdomyosarcoma, such as the t(1;13)(p36;q14).
Comparative genomic hybridization in the investigation of myeloid leukemias
Authors: Bentz Martin , Döhner Hartmut , Huck Karin , Schütz Barbara , Ganser Arnold , Joos Stefan , Manoir Stanislas Du , Lichter Peter 
Published: February 2007

AbstractComparative genomic hybridization (CGH) was used for the examination of ten cases of myeloid leukemia (eight acute myeloid leukemias and two myelodysplastic syndromes). In five cases, genomic gains or losses were identified, which mapped to chromosomal regions known to be involved in this group of malignancies. In comparison to the results obtained by banding analysis, discrepancies were found in three of the ten cases; in two cases, chromosomal imbalances were not identified by CGH because they were present only in small subclones. In the other case, there were no evaluable metaphase cells for banding analysis; CGH revealed an overrepresentation of chromosome 8, which was confirmed by interphase cytogenetics with a chromosome 8‐specific alphoid probe. All abnormalities revealed by CGH were confirmed by G‐banding or subsequent interphase cytogenetic analysis, which demonstrates the high specificity of the method. Furthermore, in all cases, CGH identified the chromosomal imbalances present in the major clone as detected by banding analysis. The good correlation between CGH and chromosome banding results in myeloid leukemias makes this tumor a good model for the assessment of tools that are developed for automated and quantitative CGH analysis.
Mutation of the RET protooncogene in sporadic medullary thyroid carcinoma
Authors: Eng Charis , Mulligan Lois M. , Smith Darrin P. , Healey Catherine S. , Frilling Andrea , Raue Friedhelm , Neumann Hartmut P. H. , Pfragner Roswitha , Behmel Annemarie , Lorenzo Maria J. , Stonehouse Timothy J. , Ponder Margaret A. , Ponder Bruce A. J. 
Published: February 2007

AbstractMedullary thyroid carcinoma (MTC) occurs sporadically or as part of the inherited cancer syndrome multiple endocrine neoplasia (MEN) type 2. In MEN 2A, germline missense mutations are found in one of five cysteine codons within exons 10 and 11 in the extracellular domain of the RET protooncogene. In MEN 2B, germline mutations occur in codon 918 (exon 16) within the catalytic core of the tyrosine kinase domain. To determine if RET mutations similar to those in MEN 2A and 2B play a role in the pathogenesis of sporadic MTC, we analysed 71 sporadic tumours comprising 68 primary tumours and three cell lines, for mutations in RET exons 10, 11, and 16. We found that 23% of sporadic MTC had RET codon 918 mutations, while only 3% had exon 10 mutations, and none had mutations in exon 11. We found no exon 16 mutations in MTC from 14 MEN 2A cases. Thus, exon 10 and 11 mutations, commonly found in familial MTC and MEN 2A, rarely occur in sporadic MTC; somatic mutation of RET codon 918 appears to play a role in the tumourigenesis of a significant minority of sporadic MTC but not MEN 2A tumours. In addition to their biological interest, these findings may have some clinical application in determining whether a patient presenting with isolated MTC is truly sporadic or is part of an inherited cancer syndrome.
Cytogenetic and histologic findings in 17 pulmonary chondroid hamartomas: Evidence for a pathogenetic relationship with lipomas and leiomyomas
Authors: Fletcher Jonathan A. , Longtine Janina , Wallace Kristin , Mentzer Steven J. , Sugarbaker David J. 
Published: February 2007

AbstractPulmonary chondroid hamartomas (PCH) are benign tumors that contain mesenchymal and epithelial components. In this series, we identified clonal chromosome aberrations in mesenchymal cells from 10 of 17 PCH. Chromosome band 12q15 was rearranged most frequently (N = 4), and one case had a t(12;14)(q15;q24) that was identical cytogenetically to the characteristic translocation in uterine leiomyomas. Histologic review revealed diverse mesenchymal populations, including undifferentiated cells, cartilage, adipose tissue, and smooth muscle, in most of the PCH. These findings suggest that PCH result from neoplastic transformation of a primitive mesenchymal cell that differentiates along chondroid, adipose, and smooth muscle pathways.
Interphase cytogenetics of prostatic adenocarcinoma and precursor lesions: Analysis of 25 radical prostatectomies and 17 adjacent prostatic intraepithelial neoplasias
Authors: Alers Janneke C. , Krijtenburg Pieter Jaap , Vissers Kees J. , Bosman Fré T. , van der Kwast Theodorus H. , Van Dekken Herman 
Published: February 2007

AbstractTwenty‐five radical prostatectomy specimens were screened for the presence of numerical chromosome changes within the adenocarcinoma as well as in 17 adjacent prostatic intraepithelial neoplasias (PIN) by means of interphase in situ hybridization (ISH) to routinely processed tissue sections. To this end a defined alfoid repetitive DNA probe set was used, specific for the centromeres of chromosomes 1, 7, 8, 10, 15, and Y. The cytogenetic information was correlated with histopathological and clinical features as well as with DNA ploidy. Numerical aberrations of at least one chromosome were shown in 13 of 25 cases (52%). Alterations of chromosome 8 and loss of the Y chromosome were the most frequent findings (both 20%), followed by loss of chromosomes 15 (16%) and 10 (12%). Gain of chromosome 7 was seen in 8% of cases. No aberrations of chromosomes 7, 8, 10, and 15 were found in the adjacent PIN lesions, whereas loss of the Y chromosome in both PIN and tumor occurred in two cases. Also, (low level) aneuploidy was observed in 76% of these PIN lesions. Ploidy of the carcinomas as assessed by ISH correlated well with ploidy measured by DNA flow cytometry (FCM; P < 0.02). Due to the more specific correspondence between ISH and tumor pathology, pathologic grade correlated with ISH aneuploidy (P < 0.05), whereas FCM ploidy did not. Furthermore, genetic heterogeneity within a tumor was seen, as judged by the focal appearance of chromosomal aberrations. Chromosomal alterations occurred in all grades and stages, although loss of chromosome 10, gain of chromosome 7, and aberrations of chromosome 8 tended to predominate in more advanced cancers.
Suppression of endometrial carcinoma cell tumorigenicity by human chromosome 18
Authors: Yamada Hideto , Sasaki Masahiro , Honda Tsuyoshi , Wake Norio , Boyd Jeff , Oshimura Mitsuo , Barrett J. Carl 
Published: February 2007

AbstractPresumptive tumor suppressor genes may be localized to specific chromosomes by the procedure of microcell fusion, whereby individual chromosomes derived from normal human cells are introduced into tumor cells. Allelic loss on chromosome I 8 is commonly seen in endometrial carcinoma, and the DCC gene on chromosome arm 18q is a potential human tumor suppressor gene. In this study, we investigated the hypothesis that a gene on chromosome 18, possibly DCC, is capable of suppressing the tumorigenicity of endometrial carcinoma cells. Microcells from the mouse A9 cell clone containing one human chromosome I8 tagged with the pSV2‐neo plasmid were fused with the highly tumorigenic endometrial carcinoma cell lines HHUA and Ishikawa, and G418‐resistant microcell hybrids containing an extra copy of chromosome I8 were isolated. Clones isolated from the HHUA cell line were completely suppressed for tumorigenicity in nude mice, and clones from the lshikawa line were suppressed or inhibited for tumorigenicity. In contrast, growth rates in vitro were not significantly affected in clones from either parental cell line. DCC expression was elevated in most of the suppressed hybrids. These results indicate that a gene on human chromosome I 8 is capable of suppressing the tumorigenicity of endometrial carcinoma cells, and that DCC is a candidate for this endometrial carcinoma tumor suppressor gene. © 1995 Wiley‐Liss, Inc.
dic(9; 20): A new recurrent chromosome abnormality in adult acute lymphoblastic leukemia
Authors: Rieder Harald , Schnittger Susanne , Bodenstein Heinrich , Schwonzen Martin , Wörmann Bernhard , Berkovic Dinko , Ludwig Wolf‐Dieter , Hoelzer Dieter , Fonatsch Christa 
Published: February 2007

AbstractLoss of chromosome 20 and rearrangement of the short arm of chromosome 9 were identified by banding analysis of three adult patients with acute lymphoblastic leukemia (ALL). The G‐banding pattern suggested and identical deletion of 9p, but, also, an unbalanced translocation with chromosome 20 was taken into consideration. Dual‐color chromosome painting with probes for chromosomes 9 and 20 revealed the presence of material from chromosome 20 at the short arm of the abnormal chromosome 9 in all three cases. Centromeric alpha‐satellite DNA of both chromosome 9 and chromosome 20 was demonstrated by fluorescence in situ hybridization and indicated the presence of a dicentric chromosome. The hybridization of a YAC clone of the short arm of chromosome 20 proved that the dicentric chromosome contained the short arm of chromosome 20, which had been suspected from the G‐banding pattern. Thus, the rearrangement was interpreted as dic(9; 20)(pl I;qi I . ? I). Because this was the sole chromosome abnormality in two patients, dic(9; 20) may be a primary chromosome aberration in ALL. In one case, a 9q+ chromosome derived from a Philadelphia (Ph) translocation was involved in the formation of the dicentric chromosome. Immunophenotyping revealed CD 1o+ B‐cell precursor ALL in all three cases. Whereas the two patients in whom dic(9; 20) was the sole cytogenetically detectable change are in continuous complete remission for 10 and 45 months, respectively, the Ph+ patient relapsed with leukemia and died 8 months after diagnosis. © 1995 Wiley‐Liss, Inc.
Involvement of chromosomes 17 and 22 in dermatofibrosarcoma protuberans
Authors: Minoletti Fabiola , Miozzo Monica , Pedeutour Florence , Sard Laura , Pilotti Silvana , Azzarelli Alberto , Turc‐Carel Claude , Pierotti Marco A. , Sozzi Gabriella 
Published: February 2007

AbstractLiterature on the cytogenetics of dermatofibrosarcoma protuberans (DFSP) is limited; only I0 cases with chromosome aberrations have been reported. They are karyotypically characterized by the presence of supernumerary ring(s), either as the sole cytogenetic abnormality or together with a few additional structural or numerical changes. We report the cytogenetic and fluorescence in situ hybridization (FISH) analysis of three new DFSP, one primary and two recurrent tumors. In two cases we found a supernumerary ring as the sole change, whereas the third had two copies of a marker chromosome and monosomy of chromosome 22. Sequences of chromosomes I7 and 22 were identified by FISH in the supernumerary rings and in the markers. The fluorescence pattern suggested that additional sequences were present in the two rings, but showed that the marker chromosomes were entirely painted by chromosome 17 and 22 probes. The findings indicate that juxtaposition and/or amplification of chromosome 17 and 22 sequences could be crucial in the pathogenesis of DFSP. © 1995 Wiley‐Liss, Inc.
Cytogenetic and molecular studies on the neuroblastoma cell line NGP: Identification of a reciprocal t(I;I5) involving the “consensus region” Ip36. I
Authors: Muresu Rosella , Casciano Ida , Volpi Emanuela V. , Siniscalco Marcello , Romani Massimo 
Published: February 2007

AbstractA reciprocal t(I; 15)(p36.1–36.3;q25‐26) has been identified in an established neuroblastoma cell line (NGP) that earlier studies had shown to carry, among others, a rearrangement at the Ip subtelomeric region. Though it has not been possible to establish whether this translocation was constitutional, it is of interest to note that one of the breakpoints is located within the well‐known Ip consensus site of tumor‐associated chromosomal rearrangements where, as a result of the reciprocal translocation, the FES oncogene has been transferred from autosome IS. It is to be expected that the molecular cloning of the I p and I 5q translocation breakpoints may yield crucial data for understanding the association between specific chromosomal rearrangements and malignant tumor progression.