bluuebunny/crossref_metadata_2025 huggingface dataset:
Loss of heterozygosity in asbestos‐induced mutations in a human mesothelioma cell line
Authors: Both Katrin , Turner David R. , Henderson Douglas W.
Published: February 2007

The relationship between occupational or environmental exposure to asbestos and the development of mesothelioma, typically after prolonged latency, has been accepted as one of cause and effect. Most studies have concluded that asbestos is not mutagenic to mammalian cells in vitro. We have studied the potential of crocidolite asbestos to induce mutations in a stable mesothelioma cell line, using a mutation assay that measures mutation at the autosomal HLA‐A locus and permits clonal growth of mutant cells. The mesothelioma cell line chosen is more akin to the in vivo target cells of asbestos than human peripheral blood lymphocytes used in previous studies. Exposure of mesothelioma cells in culture to both 200 μg/ml and 50 μg/ml crocidolite for 72 hr did not result in a statistically significant difference in the mutation frequency (MF) in the HLA‐A assay when compared to the spontaneous MF in these cells. Mutations in the mesothelioma cells were classified according to their molecular basis. Notwithstanding the lack of statistically significant change in overall MF, molecular analysis of mutants obtained following exposure of mesothelioma cells to crocidolite demonstrated a statistically significant increase in the class of mutations arising from loss of heterozygosity (LOH) events involving the selection locus (HLA‐A) and more distal loci. Mutations following exposure to 200 μg/ml and 50 μg/ml crocidolite showed a greater frequency of LOH than did spontaneous mutants (P < 0.01 and P < 0.001, respectively). These results correlate with those obtained in an earlier study using lymphocytes. The mesothelioma cell‐based assay may be useful in detecting the mutagenicity of other asbestiform fibers and man‐made fibers. © 1995 Wiley‐Liss, Inc.
Relationships among in vitro mutagenicity assays: Quantitative vs. qualitative test results
Authors: Benigni Romualdo , Andreoli Cristina , Giuliani Alessandro
Published: February 2007

In previous investigations, we studied the relationships between the profiles of the qualitative responses of in vitro short‐term tests (mutation in Salmonella typhimurium, chromosomal aberrations in CHO cells, sister chromatid exchanges in CHO cells, and mutation in mouse lymphoma cells) and common sets of chemicals. In this paper, we address the study of the quantitative responses (potency). We show that two analyses point to similar patterns of relationships: the mutation in mouse lymphoma cells assay is most similar to the CHO sister chromatid exchange assay, and the Salmonella assay is most similar to the CHO chromosomal aberrations assay. © 1995 Wiley‐Liss, Inc.
Genotoxic effects of p‐aminophenol in chinese hamster ovary and mouse lymphoma cells: Results of a multiple endpoint test
Authors: Majeska Jenness B. , Holden Henry E.
Published: February 2007

p‐Aminophenol (PAP), a metabolite of aniline and acetaminophen, has been reported to be mutagenic in the L5178Y mouse lymphoma assay, but not in the CHO/HGPRT assay. In the present study, the effects of PAP in these two cells lines were examined to determine if the difference in activity is related to an intrinsic difference in the cell lines. CHO and L5178Y +/− mouse lymphoma cells were treated with PAP for 4 hr and assayed for 3 genetic endpoints: gene mutation at the HGPRT or TK locus, respectively; chromosomal aberrations at approximately 20 hr after initiation of treatment; and single‐stand DNA breaks as detected by the single cell electrophoresis assay immediately after treatment. All treatments were conducted in the absence of S9. There was a dose‐related, significant increase in TFT‐resistant mouse lymphoma cells at dose levels that reduced survival to ⩽=50% of concurrent controls. In CHO cells, however, there was no increase in thioguanine‐resistant cells at dose levels that reduced cell survival to < 20%. These results are consistent with published reports on PAP. While the CHO cells were slightly more resistant to the toxic effects of PAP, the dose levels used in the two cell lines did not differ by more than 2‐fold. At equivalent survival levels, PAP induced a significant (up to 20% aberrant cells) number of aberrations, primarily complex rearrangements, in both cell lines. In the single cell electrophoresis assay, there was a reproducible dose‐related increase in cells with single‐strand DNA breaks with both the L5178Y cells and the CHO cells. The induction of single‐strand breaks and chromosome aberrations by PAP suggests that, mechanistically, PAP produces similar genetic damage in both CHO and L5178Y cell lines, but intrinsic differences between assay systems are responsible for the divergent gene mutation results. © 1995 Wiley‐liss, Inc.
Atrazine treatment potentiates excretion of mutagenic urine in 2, 6‐dinitrotoluene‐treated fischer 344 rats
Authors: George S. E. , Chadwick R. W. , Kohan M. J. , Allison J. C. , Warren S. H. , Williams R. W.
Published: February 2007

Atrazine (ATZ), an s‐triazine herbicide, is a widespread environmental contaminant. The hepatocar‐cinogenic component of technical grade dinitrotoluene, 2, 6‐dinitrotoluene (2, 6‐DNT, 19.5%), is a byproduct of trinitrotoluene synthesis and is found at production sites. This study explores the effect of ATZ treatment on the bioactivation of the promutagen, 2, 6‐DNT. Male Fischer 344 rats (5 weeks old) were administered 50 mg/kg of ATZ by gavage for 5 weeks. At 1, 3, and 5 weeks, both DMSO‐control and ATZ‐pretreated rats were treated p.o. with 75 mg/kg of 2, 6‐DNT and were housed in metabolism cages for urine collection. Sulfatase‐and β‐glucuronidase‐treated, concentrated urine was bioassayed for urinary mutagens in a microsuspension modification of the Salmonella assay with and without metabolic activation. No significant change in mutagen excretion was observed in ATZ‐treated rats; however, an elevation in direct‐acting urine mutagens from rats receiving ATZ and 2, 6‐DNT at weeks 1 (359 ± 68 vs. 621 ± 96 revertants/ml) and 5 (278 ± 46 vs. 667 ± 109 revertants/ml) of treatment was observed. The increase in production of urinary mutagens was accompanied by an elevation in small intestinal nitroreductase activity. Increases in large intestinal nitroreductase and β‐glucuronidase were observed after 5 weeks. There was no apparent effect of ATZ following 5 weeks of treatment on the production of 2, 6‐DNT‐derived hepatic DNA adducts. ATZ treatment modifies intestinal enzymes responsible for promutagen bioactivation, and potentiates the excretion of mutagenic urine in 2, 6‐DNT‐treated animals. © 1995 Wiley‐liss, Inc.

This article i s a US Government work and, as such, i s in the public domain in the United States of America.
Induction of kinetochore‐containing micronuclei by exogenous 06‐methylguanine requires conversion of the methylated base to a nucleotide
Authors: Bonatti Stefania , Aprile Anna , Arena Giuseppe , Cavalieri Zita , Pellerano Paola , Rocco Mattia , Sailer Klaus , Viaggi Silvia , Abbondandolo Angelo
Published: February 2007

It has been reported that exogenous alkylated purines, such as O6‐methylguanine (O6meG), induce aneuploidy in mammalian cells. It is shown here that the aneugenic effect of O6meG, evidenced by its ability to induce micronuclei in rodent cells, is dependent on its conversion to O6‐methyl‐guano‐sine‐5′‐monophosphate (O6me‐5′‐GMP) by hypo‐xanthine‐guanine phosphoribosyl transferase (HPRT). This conclusion, in contrast with previous in vitro data showing that O6meG does not seem to be a substrate for HPRT, was based on the following observations: 1) O6meG did not induce micronuclei in HPRT‐deficient Chinese hamster cells, but did induce micronuclei in HPRT‐proficient cells, and in mouse cells partially or totally deficient in adenine phosphoribosyl transferase; 2) O6meG was not metabolized in HPRT‐deficient cells, while in wild‐type cells a number of metabolites were detected by high performance liquid chromatography (HPLC) analysis of cold acid extracts, one of them coeluting with O6me‐5′‐GMP used as a marker; 3) when de novo synthesis of purine nucleotides was inhibited by aminopterin, O6meG sustained the growth of HPRT‐proficient, but not of HPRT‐deficient, cells; and 4) when HPRT‐deficient cells were treated with lipo‐somes charged with O6me‐5′‐GMP, induction of micronuclei was shown. The finding that methylated guanine exerts its aneugenic action through methylated nucleotide(s) provides an important, though indirect, support to the hypothesis that alkylating agents may induce aneuploidy via nucleotide pool alkylation. © 1995 Wiley‐Liss, Inc.
Energy relaxation method for chemical non‐equilibrium flow computations
Authors: Patil M. M. , Mandal J. C. , Swaminathan S.
Published: February 2007

In this paper, an algorithm for chemical non‐equilibrium hypersonic flow is developed based on the concept of energy relaxation method (ERM). The new system of equations obtained are studied using finite volume method with Harten–Lax–van Leer scheme for contact (HLLC). The original HLLC method is modified here to account for additional species and split energy equations. Higher order spatial accuracy is achieved using MUSCL reconstruction of the flow variables with van Albada limiter. The thermal equilibrium is considered for the analysis and the species data are generated using polynomial correlations. The single temperature model of Dunn and Kang is used for chemical relaxation. The computed results for a flow field over a hemispherical cylinder at Mach number of 16.34 obtained using the present solver are found to be promising and computationally (25%) more efficient. The present solver captures physically correct solution as the entropy conditions are satisfied automatically during the computations. Copyright © 2007 John Wiley & Sons, Ltd.
Secondary nonrandom chromosomal abnormalities of band 13q34 in burkitt lymphoma‐leukemia
Authors: Berger Roland , le Coniat Maryvonne , Derré Josette , Vecchione Danielle
Published: February 2007

Clonal abnormalities of the long arm of chromosome 13 were detected in 9 of 54 patients with Burkitt lymphoma‐leukemia. All abnormalities involved band 13q34, in three patients as t(1;13). The 13q34 abnormalities are thus the second most frequent secondary chromosomal abnormalities, after those of chromosome 1, in these lymphoid proliferations.
Human PDGFA receptor gene maps to the same region on chromosome 4 as the KIT oncogene
Authors: Stenman Göran , Eriksson Anders , Claesson‐Welsh Lena
Published: February 2007

The gene for the human platelet‐derived growth factor (PDGF) A type receptor was assigned to the proximal long arm of chromosome 4 by using in situ hybridization. Of 141 labeled metaphase cells, 74 had grains over chromosome 4, with a distinct peak at bands q11q–q12. The presence of the gene on chromosome 4 was also confirmed by hybridization to chromosome specific libraries. This places the PDGFA receptor gene in the same region of chromosome 4 as the KIT oncogene, another member of the PDGF growth factor receptor subfamily. The two other members of this gene family, the PDGFB receptor and the colony stimulating factor‐1 (CSF1) receptor, are closely linked on the distal half of the long arm of chromosome 5.
Mutational analysis of human NRAS genes in malignant melanoma: Rapid methods for oligonucleotide hybridization and manual and automated direct sequencing of products generated by the polymerase chain reaction
Authors: Dicker Adam P. , Volkenandt Matthias , Albino Anthony P.
Published: February 2007

Three methods to detect single base mutations in codon 61 of the human NRAS gene from human melanoma DNA are described and compared: oligonuceotide hybridization analysis and direct manual and automated sequence analysis. Point mutations are detected by oligonucleotide hybridization and direct manual and direct automated sequence analysis of in vitro amplified genomic DNA. Heterozygosity for mutant alleles is reliably detected by oligonucleotide hybridization and by direct manual, but not by direct automated, sequence analysis. Generating single‐stranded DNA via “asymmetric polymerase chain reaction (PCR)” and utilizing α35S‐dATP as radiolabel for manual sequencing and fluorescent‐dye labeled primers for automated sequencing (Applied Biosystems, Inc.), we can obtain sequence information from either strand. The use of several of these methodologies to detect single base changes in the human NRAS gene is illustrated. In addition, the use of these and other related techniques to define the involvement of RAS oncogenes in human melanomas more precisely is reviewed.
Molecular analysis of the t(1;19) breakpoint cluster region in pre‐b cell acute lymphoblastic leukemias
Authors: Mellentin Julia O. , Nourse Jamison , Hunger Stephen P. , Smith Stephen D. , Cleary Michael L.
Published: February 2007

The t(1;19) chromosomal translocation in acute lymphoblastic pre‐B cell leukemias involves the gene E2A for helix‐loop‐helix (HLH) proteins E12 and E47, ubiquitous transcriptional proteins implicated in the regulation of various lymphoid and nonlymphoid genes. To characterize the molecular features of the t(1;19)(q23;p13) translocation, we molecularly cloned breakpoint DNA from t(1;19)‐carrying pre‐B cell leukemias. In all cases, breakpoints on chromosome 19 occurred within 2 kb of each other in a single intron of the E2A gene. This clustered arrangement resulted in specific truncation of the E2A gene and transcript, with loss of sequences encoding the basic DNA‐binding and HLH dimerization motifs from the derivative 19 chromosome. In contrast, breakpoints on chromosome 1 were distributed over a large region and could not be linked to exonic sequences of the PBX1 gene, although identical chromosome 1 sequences are joined to E2A sequences in 1;19 fusion transcripts. These data show that the 1;19 translocation consistently results in exchange of 3′ exons encoding the HLH motifs of E2A with DNA from chromosome 1 to form a fusion gene on the derivative 19 chromosome.
Coamplification of simple repetitive DNA fingerprint fragments and the EGFR gene in human gliomas
Authors: Nürnberg Peter , Zischler Hans , Fuhrmann Eike , Thiel Gundula , Losanova Tanka , Kinzel Dieter , Nisch Gunter , Witkowski Regine , Epplen Jörg T.
Published: February 2007

DNA fingerprints were generated by the oligonucleotide probe (GTG)5 from surgically removed tissue and/or primary cell culture of 36 intracranial tumors (31 gliomas, I medulloblastoma, 4 metastatic carcinomas) and compared with the constitutional banding pattern obtained from the peripheral blood leukocytes of each patient. A multitude of somatic changes was detected and found to reflect the chromosome alterations identified by parallel karyotype analysis. Gain and/or loss of bands or significant band intensity shifts could be demonstrated in the fingerprints of more than 80% of the tumors investigated. This included a highly amplified fingerprint fragment in five independent gliomas (four of them had double minutes, dmin) which appeared not individual‐ but tumor‐specific (2.4 kilobases, kb, after Haell digestion). Rehybridization with the oligonucleotide probes (GT)8 and (GATA)4, respectively, revealed additional amplified fingerprint fragments in the tumor DNA of these patients. While a (ca/gt)n fragment (2.6 kb. HaeIII) was also found to be amplified in all five cases, one band detected with (GATA)4 ( 1.4 kb, HaeIII) represented a unique feature for one of these tumors only. Amplification of the epidermal growth factor receptor (EGFR) gene via Southern blot hybridization was revealed only in those tumors showing the amplified DNA fingerprint fragments as well. Thus in many gliomas the amplification unit harbors two simple repetitive DNA fingerprint loci, (cac/gtg)n and (ca/gt)n, in addition to the EGFR gene.
Nonrandom structural and numerical chromosome changes in non‐small‐cell lung cancer
Authors: Whang‐Peng J. , Knutsen T. , Gazdar A. , Steinberg S. M. , Oie H. , Linnoila I. , Mulshine J. , Nau M. , Minna J. D.
Published: February 2007

Cytogenetic studies were performed on 27 tumor cell lines (most of which were derived from metastatic lesions) and four fresh malignant pleural and pericardia! effusions from 30 patients with non‐small‐cell lung cancer (non‐SCLC). Many clonal structural (deletions and nonreciprocal translations) and numerical abnormalities were found in each specimen. Statistical analysis revealed these changes were nonrandomly distributed among the chromosomes. A statistically significant number of chromosomal breakpoints were seen in regions 1 q 1, 1 q3, 3p1, 3p2, 3q1, 3q2, 7q1, 13p1, 14p1, 15p1, and 17q1 when the regions were compared to the total haploid complement. In addition, when a given region was compared to other regions within the same chromosome, statistically significant numbers of breakpoints were noted for regions 1q3, 5q1, 7q1, 13p1, 14p1, 15p1, 16q2, 17q1, and 21p1. Specific chromosome bands showing the most frequent involvement in structural abnormalities were (in descending order) 3p 14.2, 3q21, 19q13, 11p15, 1q11, 7q111, 1q21, 3p23, and 3p21. The breakpoints indicate areas to look for new dominant oncogenes activated by translocations, while the areas of deletions and loss of material by nonreciprocal translocations highlight areas to search for recessive oncogenes. These cytogenetic studies represent strong evidence that multiple genetic lesions are associated with the development of metastatic lung cancer, and provide a roadmap to search for new genes involved in the pathogenesis of lung cancer.
Implication of RARB in Epidermoid (Squamous) Lung Cancer
Authors: Houle Benoit , Leduc François , Bradley W. E. C.
Published: February 2007

We report a higher frequency of loss of heterozygosity at loci on the short arm of chromosome 3 in human epidermoid lung tumors than in other non‐small cell lung tumors. This observation together with the already known involvement of the retinoids in the development of epidermoid metaplasia and neoplasia, especially in lung tissue, prompted us to investigate by RNAase protection assays the status of expression of a gene that maps on chromosome band 3p24 and codes for the B receptor for retinoic acid (RARB). We show that expression of RARB is detectable in normal lung tissue and in most of the cell lines derived from lung tumors, including the five non‐small cell lines that clearly had a non‐epidermoid phenotype. Strikingly, however, only one of the five epidermoid‐tumor‐derived cell lines studied showed detectable expression of RARB. Of two lines derived from adenosquamous tumors, one had a clear epidermoid differentiation, and this line also did not express RARB. Taken together, our results strongly implicate RARB in the evolution of epidermoid lung tumors.
Involvement of 3p Deletions in Sporadic and Hereditary Forms of Renal Cell Carcinoma
Authors: Boldog Ferenc , Arheden Kristina , Imreh Stephan , Strombeck Bodil , Szekely Laszlo , Erlandsson Rikard , Marcsek Zoltan , Sumegi Janos , Mitelman Felix , Klein George
Published: February 2007

Deletions of the short arm of chromosome 3 and associated allele losses have been reported in the majority of sporadic renal cell carcinomas (RCC). On the basis of the combined cytogenetic and molecular data, it is reasonable to assume that a putative RCC locus, which contributes to tumor development by its loss, is located telomerically of the D3F15S2 site. Using H3E4, a D3F1SS2‐specific probe, we have isolated a cDNA clone (c1.4–2), and a sequence comparison revealed that the cDNA clone corresponds to the human acyl‐peptide hydrolase gene. The gene is fairly universally expressed, but in RCC biopsies its expression is severely reduced, compared to the normal kidney. Cl.4–2 was used for in situ hybridization on metaphase chromosomes prepared from an Epstein‐Barr virus (EBV) transformed lymphoblastoid cell line, derived from a t(3;8) (p14.2;q24.1) carrying member of the RCC family described by Cohen et al. in 1979 (N Engl J Med: 301:592–595). Carriers of this translocation regularly develop RCC by middle age. We now report that D3F15S2 is localized on the telomeric side of the constitutional breakpoint, in 3p21. The region of 3p affected by this familial translocation is thus not identical with the region of 3p most frequently deleted in sporadic RCC.
t(10;11)(p13–14;q14–21): A New Recurrent Translocation in T‐Cell Acute Lymphoblastic Leukemias
Authors:   Groupe Français de Cytogénétique Hématologique (GFCH)
Published: February 2007

A workshop held by the „Groupe Français de Cytogénétique Hématologique”︁ has identified a t( 10; 11)(p13–14;q14–21) in four acute lymphoblastic leukemias of T‐cell lineage. The immunophenotypes were consistent with immature thymocytes. This translocation is therefore a new candidate for a recurrent translocation in early T‐cell leukemia. A similar translocation has been reported as a rare change in early pre‐B lymphoid leukemias and also in myeloid leukemias. It is not known whether the similar cytogenetic changes involve different molecular breakpoints or whether the same rearrangement affects a multipotential stem cell capable of lymphoid and myeloid differentiation.
The LCK Gene Is Involved in the t(1;7)(p34;q34) in the T‐Cell Acute Lymphoblastic Leukemia Derived Cell Line, HSB‐2
Authors: Burnett Robert C. , David Jean‐Claude , Harden Alanna M. , Le Beau Michelle M. , Rowley Janet D. , Diaz Manuel O.
Published: February 2007

HSB‐2 is a cell line derived from a patient who had T‐cell acute lymphoblastic leukemia (T‐cell ALL) with a t( 1;7)(p34;q34). We used a genomic probe from the T‐cell receptor beta (TCRB) locus (7q34) to identify DNA rearrangements in HSB‐2. Two rearranged Bg/11 DNA fragments were cloned, and one of these clones was shown to contain the translocation breakpoint on the derivative chromosome 1 [der(1)]. We used a probe derived from this clone to isolate an unrearranged phage clone encompassing the breakpoint at 1 p34. The restriction map of this clone was compared to the published maps of known protooncogenes located at 1 p32–34. By restriction mapping, Southern blot analysis, and DNA sequencing we showed that the translocation breakpoint on chromosome 1 is located within the first intron of the LCK gene. The LCK gene codes for p56lck, a member of the SRC family of cytoplasmic tyrosine protein kinases. There are two classes of LCK transcripts (type 1 and type 11), each expressed from a distinct promoter, and each having a unique 5′ untranslated region (UTR); the protein coding regions of the two classes are identical. The breakpoint in the t( 1;7) separates the two LCK promoters and juxtaposes the constant region of the TCRB locus with the proximal promoter and with the protein‐coding region of the LCK gene on the der(1) chromosome.
Karyotype and T‐cell receptor expression in t‐lineage acute lymphoblastic leukemia
Authors: Secker‐Walker Lorna M. , Sampson Rebecca E. , Hawkins Jacqueline M. , Campana Dario , Coustan‐Smith Elaine
Published: February 2007

The relationship between karyotype and expression of the T‐cell receptor (TCR) proteins was examined in 19 patients with T‐lineage acute lymphoblastic leukemia (T‐ALL). All patients expressed CD3 molecules in the cytoplasm or on the cell membrane. Patients were classified according to TCR expression thus: no TCR expression (TCR–), six cases; cytoplasmic expression of TCR beta chain (cTCRB) only, six cases; membrane expression of TCR alpha and beta chains (mTCRAB), five cases; membrane expression of TCR gamma and delta (mTCRGD), two cases. A chromosomally abnormal clone was detected in 15 cases. The most common site of chromosomal change was at 14q11 (seven cases), the chromosomal band to which TCRA and TCRD have been mapped; as a deletion (two cases); or as a translocation with reciprocal breakpoints in bands containing the TCRG (7p15); TCRB (7q35); or putative oncogenes HOX11 (10q24), RBTN2 (11p13), or MYC (8q24) genes. Breakpoints were also seen in 6q (three cases), 9p (two cases), or 11q23 (two cases). The following observations were made: All four chromosomally normal cases lacked TCR expression (TCR–). Breakpoints at 14q11 were found in one of six TCR – cases, four of six cTCRB cases, and two of five mTCRAB cases. Abnormalities of 6q and of 9p were seen only in cases with full TCR expression (mTCRAB or mTCRGD).
Localization of the fibroblast growth factor receptor‐4 gene to chromosome region 5q33‐qter
Authors: Armstrong Elina , Partanen Juha , Alitalo Karl , Cannizzaro Linda , Huebner Kay
Published: February 2007

Our polymerase chain reaction cloning of novel tyrosine kinases expressed in the K562 chronic myeloid leukemia cells has revealed a novel fibroblast growth factor receptor, FGFR4. We have here mapped the FGFR4 gene by analysis of somatic cell hybrids and in situ hybridization to the 5q33‐qter chromosomal region. This finding is of interest in that the FGFR4 gene is expressed in several leukemia cell lines and the 5q33‐qter region is involved in nonrandom chromosomal translocations in acute myelogenous leukemias and Ki‐ I lymphomas.
Losses of 3p, 11p, and 13q in ej/ras‐ transformable simian virus 40‐immortalized human uroepithelial cells
Authors: Kao Chinghai , Wu Shi‐Qi , Bhatthacharya Manju , Meisner Lorraine F. , Reznikoff Catherine A.
Published: February 2007

Five independent clones of Simian virus 40 (SV40)‐immortalized human uroepithelial cells (CK/SV‐HUC) were established after transfection of HUC cultures from the same tissue donor with plasmids encoding SV40 large T and small t antigen genes. Each CK/SV‐HUC clone contained a unique SV40 integration site, and all expressed similar levels of SV40 mRNA. All five clones were nontumorigenic, but clones 2, 4, and 5 tumorigenically transformed after transfection at P19 with mutant EJ/ras and also spontaneously after 40 serial passages in vitro. In contrast, CK/SV‐HUC clones 1 and 3 did not transform when either approach was used. These differences in transformability among CK/SV‐HUC clones could not be predicted based on differences in SV40 gene expression nor on any in vitro growth property tested. In cytogenetic analyses, a transformable clone showed losses of three chromosome arms containing putative cancer suppressor gene regions, including 3p14→pter, 13q, and 11p, whereas the nontransformable clones showed none of these losses. Thus these data indicate that genetic losses on 3p, 11p, and 13q may contribute to tumorigenic transformation of SV40‐immortalized human uroepithelial cells.
Amplification of the topoisomerase ii α gene in a non‐small cell lung cancer cell line and characterisation of polymorphisms at the human topoisomerase ii α and β loci in normal tissue
Authors: Nicol Keith W. , Brown Robert , Tan K. B.
Published: February 2007

DNA was prepared from normal tissue and 19 lung cancer cell lines. Using probes which detect restriction fragment length polymorphisms at both the topoisomerase II α and β loci, heterozygosity was detected at a frequency of 0.17 and 0.37 for the α and β loci, respectively. Southern blot analysis of DNA extracted from lung cancer cell lines detected amplification of both the topoisomerase II α and ERBB2 genes in the adenocarcinoma line Calu3. These results indicate that topoisomerase II α and ERBB2 may be closely linked on chromosome 17 and coamplified during adenocarcinoma progression. Since topoisomerase II is a target for several anticancer drugs, it will be of interest to study alterations to topoisomerase II genes during tumour development, as these may in part determine the response of the tumour to chemotherapy.
Trisomy 5 and trisomy 7 are nonrandom aberrations in pigmented villonodular synovitis: Confirmation of trisomy 7 in uncultured cells
Authors: Fletcher Jonathan A. , Henkle Carol , Atkins Leonard , Rosenberg Andrew E. , Morton Cynthia C.
Published: February 2007

Pigmented villonodular synovitis (PVNS) is a proliferative lesion of disputed genesis. Recently, we reported trisomy 7 in short‐term cultures of I PVNS. In the present report, we describe another specimen of PVNS in which 9 of 26 (35 percent) metaphase cells demonstrated trisomy 7 when analyzed after 3–15 days of tissue culture. In situ hybridization analysis, with a biotinylated probe to chromosome 7 alpha‐satellite DNA, revealed trisomy 7 in 53 of 200 uncultured cells from this PVNS sample. Our findings indicate that trisomy 7 is a nonrandom aberration that arises in vivo in PVNS.
Preferential chromosome loss in human papilloma virus DNA‐lmmortalized mammary epithelial cells
Authors: Swisshelm Karen , Leonard Michele , Sager Ruth
Published: February 2007

Human papilloma virus (HPV) DNA‐immortalized human mammary epithelial cells may provide a model system for studying the molecular basis of immortalization and its role in breast neoplasia. Cytogenetic analyses were performed on clones derived from HPV 16‐ and HPV 18‐immortalized human mammary epithelial cells. The majority of the clones contained near‐diploid karyotypes. The single most frequent whole‐chromosome loss was that of chromosome 19. Regions that showed preference for deletion and/or translocation included 2pter, 11qter, and 15pter. Evidence of chromosome 19 loss was confirmed by polymerase chain reaction (PCR)‐generated, chromosome 19‐specific, dinucleotide microsatellite repeat polymorphism analysis.
Detection of recurrent chromosome abnormalities in Ewing's sarcoma and peripheral neuroectodermal tumor cells using bivariate flow karyotyping
Authors: Boschman Gert A. , Rens Wim , Manders Erik M. M. , Slater Rosalyn M. , Versteeg Rogier , Aten Jacob A.
Published: February 2007

Bivariate flow karyotyping can be used for the detection of recurrent chromosome abnormalities in tumor cells. For this purpose 2 cell lines originally derived from Ewing's sarcomas and 4 cell lines from peripheral neuroectodermal tumors were used. The characteristic t(11;22) was known to be present in 5 cell lines. The remaining cell line was known to have a variant t(2;11;22;21) translocation. Metaphase chromosomes were stained with the fluorescent dyes Hoechst 33258 and Chromomycin A3 and analyzed subsequently using bivariate flow cytometry. The resulting bivariate flow karyotypes of the tumor cells were normalized by a standardized procedure using a computerized method and compared with a reference flow karyotype of normal chromosomes. In 5 cell lines two recurring abnormal chromosome peaks were identified at positions expected for the der(11) and der(22) chromosomes characteristic for the reciprocal t(11;22)(q24;q12). In the remaining cell line with the variant t(2;11;22;21), only the peak representing the der(22) was identifiable. It is concluded that bivariate flow karyotyping can be used for the semiautomated detection of recurrent translocations and the assessment of their variability among different tumors. © 1992 Wiley‐Liss, Inc.
DNA fingerprinting of renal cell carcinoma with special reference to tumor heterogeneity
Authors: Mehle Christer , Ljungberg Börje , Stenling Roger , Roos Göran
Published: February 2007

Genomic alterations in renal cell carcinoma were investigated by DNA fingerprinting using the simple repetitive oligonucleotide probe (CAC)5. Nine of ten tumors showed somatic changes in the fingerprint pattern compared with constitutional DNA. The most consistent changes were deletions and/or decrease in intensity of a band. When using two or three samples from different parts within the tumor, up to three different cell clones could be detected. These results indicate that DNA fingerprinting analysis can be a useful technique for the study of genomic alterations and tumor heterogeneity in renal cell carcinoma. © 1993 Wiley‐Liss, Inc.
Identification of a yeast artificial chromosome (YAC) spanning the synovial sarcoma‐specific t(X;18)(p11.2;q11.2) breakpoint
Authors: De Leeuw B. , Berger W. , Sinke R. J. , Suijkerbuijk R. F. , Gilgenkrantz S. , Geraghty M. T. , Valle D. , Monaco A. P. , Lehrach H. , Ropers H. H. , Van Kessel A. Geurts
Published: February 2007

A somatic cell hybrid containing the synovial sarcoma‐associated t(X;18)(p11.2;q11.2) derivative (der(X)) chromosome was used to characterize the translocation breakpoint region on the X chromosome. By using Southern hybridization of DNA from this der(X) hybrid in conjunction with Xp‐region specific radiation reduced cell hybrids and probes, it was found that this breakpoint maps within the ornithine aminotransferase (OAT) L1 cluster. A yeast artificial chromosome (YAC) clone (OAT YAC2) which hybridizes to a human OAT cDNA probe and is known to contain part of the OATL1 cluster was selected and used to confirm these results both by fluorescence in situ hybridization on synovial sarcoma patient material and by hybridization of its end‐clones to the der(X) containing hybrid cells. It was found that indeed the human Xp sequences contained within this YAC are split as a consequence of the (X;18) translocation. Therefore, we conclude that OAT YAC2 spans the synovial sarcoma‐specific translocation breakpoint and, as such, may serve as an ideal starting point from which the gene(s) involved in the development of this soft tissue tumor can be isolated. © 1993 Wiley‐Liss, Inc.
Allelic loss at chromosome band 8p21.3‐p22 is associated with progression of hepatocellular carcinoma
Authors: Emi Mitsuru , Fujiwara Yoshiyuki , Ohata Hiroyuki , Tsuda Hitoshi , Hirohashi Setsuo , Koike Morio , Miyaki Michiko , Monden Morito , Nakamura Yusuke
Published: February 2007

Human hepatocellular carcinomas (HCC) frequently show loss of heterozygosity at loci on the short arm of chromosome 8. To define a region on 8p commonly deleted in HCC, we used 20 restriction fragment length polymorphism markers to carry out detailed deletion mapping in 142 HCC. Of the 124 informative cases, 56 (45%) showed allelic losses in tumors. While more than half of them had lost alleles at every locus on the short arm, others lost them partially or interstitially. Common deletion of an 8‐cM region flanked by cMSR‐32 and cC18‐245, at 8p21.3‐p22, suggested the presence of a tumor suppressor gene(s) in this interval. Correlation between allelic losses on 8p and clinicopathological parameters were examined in the 51 cases for which detailed clinical data were available; allelic losses on 8p were observed in none of five tumors at stage T1 (0%), nine of 20 tumors at stage T2 (45%), and 17 of 26 tumors at stage T3/T4 (65%). A higher frequency of allelic losses on 8p was observed in poorly differentiated tumors (10/14, 71%) than in well differentiated tumors (3/13, 23%). The association of allelic losses on 8p with advanced clinical stage and poor differentiation implies that loss or inactivation of a tumor suppressor gene(s) on 8p may play a role in the progression of HCC. © 1993 Wiley‐Liss, Inc.
Loss of heterozygosity in malignant melanoma at loci on chromosomes 11 and 17 implicated in the pathogenesis of other cancers
Authors: Tomlinson I. P. M. , Gammack A. J. , Stickland J. E. , Mann G. J. , Mackie R. M. , Kefford R. F. , McGee J. O'D.
Published: February 2007

Forty‐six cases of sporadic melanoma have been investigated for loss of heterozygosity at 4 loci: D11S29 (11q23), YNZ22 (17p13.3), TP53 (17p13.1); and NM23 (17q22). Each of the loci is thought to be important in the pathogenesis of other tumours. Mutations were found infrequently at the YNZ22, NM23, and TP53 loci. At D11S29, however, the frequency of mutation in the melanoma samples was high (67%) and mutations at this locus were associated with younger age at presentation. This region of chromosome 11 is also commonly mutated in breast cancers and haematological malignancies. Genetic aberrations at D11S29 may therefore represent nonspecific mutations found in several malignancies or part of a pathway common to the malignant phenotype. © 1993 Wiley‐Liss, Inc.
Near‐haploid karyotype in a squamous cell lung carcinoma
Authors: Drouin Valérie , Viguié Franck , Debesse Bernard
Published: February 2007

Cytogenetic analysis of a squamous cell lung carcinoma revealed a near‐haploid karyotype with 27 chromosomes, in both primary cultures and an established cell line. The only chromosomes with two homologs present were chromosomes X, 5, 7, and 22. The two X chromosomes were early and late replicating, respectively. No structural rearrangements could be detected. In vitro, the clone evolved by duplication towards hyperdiploidy with 54 chromosomes. © 1993 Wiley‐Liss, Inc.
Mapping of the gene for interferon‐inducible dsRNA‐dependent protein kinase to chromosome region 2p21‐22: A site of rearrangements in myeloproliferative disorders
Authors: Hanash Samir M. , Beretta Laura , Barcroft Christine L. , Sheldon Susan , Glover Thomas W. , Ungar David , Sonenberg Nahum
Published: February 2007

Recent evidence suggests that the human interferon‐inducible double‐stranded RNA‐dependent protein kinase may function as a tumor suppressor. Here we describe the mapping of the gene for this kinase to chromosome region 2p21‐22 by fluorescence in situ hybridization. A combined analysis of cytogenetic data from a series of 341 patients with hematologic disorders that exhibited cytogenetic abnormalities and from published reports indicates that abnormalities involving 2p21‐22 occur nonrandomly and are observed among patients with acute myelogenous leukemia, raising the possibility of a role for this protein kinase in leukemogenesis. © 1993 Wiley‐Liss, Inc.
In situ hybridization to interphase nuclei in acute leukemia
Authors: Romana Serge P. , Cherif Dorra , Coniat Maryvonne Le , Derré Josette , Flexor Marie‐Ange , Berger Roland
Published: February 2007

Numerical chromosome abnormalities were studied in 17 acute lymphoblastic leukemias and one hyperdiploid acute myeloblastic leukemia by fluorescence in situ hybridization (FISH) using YAC clones specific to chromosomes 21 and 6. The results agreed well with cytogenetic findings. Hyperdiploid leukemias with more than 50 chromosomes usually had 4 copies of chromosome 21 and three of chromosome 6, while diploid and pseudodiploid cases were confirmed to have two copies of the two chromosomes. Interesting discrepancies were also observed. In one patient, trisomy 6 was detected by FISH but not by cytogenetics because of the probable inclusion of a chromosome 6 segment within a marker chromosome. The percentages of nuclei with 3 or 4 spots (chromosome 21) and three spots (chromosome 6) in hyperdiploid cells were significantly different in some patients, whereas they might be identical from cytogenetic data. © 1993 Wiley‐Liss, Inc.
Integration site of human papillomavirus type‐18 DNA in chromosome band 8q22.1 of C4‐1 cervical carcinoma: DNase I hypersensitivity and methylation of cellular flanking sequences
Authors: Gallego Marta I. , Lazo Pedro A. , Zimonjic Drazen B. , Popescu Nicholas C. , Dipaolo Joseph A.
Published: February 2007

The C4‐1 cell line derived from a non‐keratinizing squamous cell carcinoma of the uterine cervix contains integrated human papillomavirus‐18 DNA. Fluorescence in situ hybridization of C4‐1 cells demonstrated a single viral integration site at 8q22.1 on a derivative chromosome originating from an 8q; 12q translocation. 8q22 is a site of chromosome fragility and is also recombinogenic in several human malignancies. DNase I hypersensitivity of the integration site was studied with a cellular flanking probe. A hypersensitive site was detected within 3 kb from viral DNA. The integration sites are undermethylated in C4‐1 and HeLa cells and fully methylated in tumor cell lines of other origin, such as lymphoid cells. Genes Chrom Cancer 9:28‐32 (1994). © 1994 Wiley‐Liss, Inc.
Rhabdoid tumor of the kidney with primitive neuroectodermal tumor of the central nervous system: Associated tumors with different histologic, cytogenetic, and molecular findings
Authors: Fort Daniel W. , Tonk Vijay S. , Tomlinson Gail E. , Timmons Charles F. , Schneider Nancy R.
Published: February 2007

Rhabdoid tumor of the kidney (RTK) is associated with tumors of the central nevous system (CNS) in approximately 15% of cases. We describe the clinical features, histologic and cytogenetic findings, and molecular analysis of renal and CNS tumors from the same patient. The histology of the renal tumor was consistent with rhabdoid tumor. The CNS tumor was a primitive neuroectodermal tumor (PNET). The karyotype of the RTK was normal male. The PNET of the brain demonstrated monosomy 22 as the only cytogenetic abnormality, similar to reported cases of malignant rhabdoid tumor of the brain, but dissimilar to nonrandom cytogenetic findings in other CNS PNETs. Molecular cytogenetic and DNA marker studies confirmed loss of chromosome 22 in this patient's brain tumor. DNA allelotyping showed retention of both parental chromosome 22 alleles in the RTK and loss of the maternal allele in the PNET. Evaluation of additional RTKs and brain tumors occurring in the same patient may provide insight into the origins and relationships of these enigmatic tumors.
Cytogenetic analysis of 63 non‐small cell lung carcinomas: Recurrent chromosome alterations amid frequent and widespread genomic upheaval
Authors: Testa Joseph R. , Siegfried Jill M. , Liu Zemin , Hunt Jay D. , Feder Madelyn M. , Litwin Samuel , Zhou Jian‐Yuan , Taguchi Takahiro , Keller Steven M.
Published: February 2007

A detailed cytogenetic analysis of 63 non‐small cell lung carcinomas (NSCLCs) was carried out for identification of recurrent chromosomal alterations. Most specimens displayed very complex karyotypes with multiple numerical and structural changes (median number, 31). Losses of chromosomes 9 (65% of cases) and 13 (71%) were the most frequent numerical changes. Loss of the Y was often observed in tumors from males. Gain of chromosome 7 was also frequent (41%). Chromosome arms 1p, 1, 3p, 3q, 6q, 7q, 8q, 9p, 11q, 17p, and 19q were particularly prone to rearrangement. The chromosome arm most often contributing to losses was 9p (79%). Other arms that were frequently lost included 3p, 6q, 8p, 9q, 13q, 17p, 18q, 19p, 21q, 22q, and the short arm of each acrocentric chromosome. The percentage of cases with loss of 3p was significantly higher in squamous cell carcinomas (94%) than in adenocarcinomas (60%). There was also a statistically significant increase in the proportion of cases with gains of 1q, 7p, and 11q in adenocarcinomas compared to squamous cell carcinomas. Several recurrent isochromosomes and unbalanced exchanges were found. Among these was i(5p), which was observed in nine tumors, eight of which displayed adenomatous features. An i(8q) was identified in six cases, including five adenocarcinomas. Double minutes and/or homogeneously staining regions were seen in seven specimens. These data indicate that numerous chromosome alterations contribute to the pathogenesis of NSCLC and that, amid this widespread genomic disarray, recurrent abnormalities exist that could have biological and clinical implications.
Use of a linear stapler in excision of Zenker's diverticulum
Authors: Talmi Yoav P. , Finkelstein Yehuda , Sadov Rima , Shvili Ytzhack , Zohar Yuval
Published: February 2007

Zenker's diverticulum is an outpouching of the hypopharyngeal wall through a triangular area of weakness in the inferior pharyngeal constrictor muscle. The current treatment of choice is a one‐stage diverticulectomy, with or without a cricopharyngeal myotomy. Closure of the esophagus after diverticulectomy by conventional suturing techniques may be somewhat difficult and time consuming. In the past 2 decades, use of stapling devices has been suggested in four reports, the largest being a series of four patients. We have used the Proximate disposable linear stapler in seven cases of Zenker's diverticulectomy with excellent results. Operation time was shortened, patient recovery hastened, and no complications were seen. We recommend the use of the stapling device in excision of Zenker's diverticulum.
Metastases to and from the upper aerodigestive tract in the population of Rochester, Minnesota, 1935‐1984
Authors: Bouquot J. E. , Weiland L. H. , Kurland L. T.
Published: February 2007

The present investigation is the first population‐based study to provide incidence and clinicopathologic data for metastases to and from the upper aerodigestive tract (UAT). In a patient cohort with relatively minimal referral bias it was determined that cervical and distant metastases occurred in 21% and 2%, respectively, of UAT carcinomas by the time of diagnosis; incidence rates per 100,000 person‐years for cervical and distant metastases from UAT carcinomas were 2.8 and 0.3, respectively; occult primary lesions represented 3.8% of all UAT carcinomas; 3.6% of all invasive UAT carcinomas were actually metastatic from another body site; and the clinicopathologic literature has overestimated the prevalence of metastases at diagnosis relative to UAT carcinomas.
Local immune reaction in nasopharyngeal carcinoma, with special reference to its prognostic evaluation
Authors: Hsu Mow‐Ming , Hsu Hey‐Chi , Lui Louis T.
Published: February 2007

A study of the tumor—host interaction was conducted in 30 patients with nasopharyngeal carcinoma (NPC). The local immune reaction was investigated by an immunoperoxidase technique using monoclonal antibodies. Eighteen patients who were clinically suspected to have NPC, but finally proved otherwise, served as controls. There was a significant difference between the number of NPC patients with interleukin‐2 receptor (IL‐2R)‐positive cells (activated T lymphocytes) in the stroma compared with the control. IL‐2R positive cells were found in 67% of NPC patients but in only 22% of controls (P< 0.01). There was a greater infiltration of T lymphocytes in patients with a good outcome compared with patients with a poor outcome. This trend was observed in both the parenchyma (60.2 versus 29.4 × 104cells/mm2) and the stroma (74.7 versus 44.8 × 104cells/mm2). The levels of Leu‐3 positive cells (helper/inducer) in the NPC parenchyma were inversely correlated to the extent of the primary tumor, but there was no correlation in the stroma. These findings demonstrate that a local host‐immune reaction does exist and may be a useful prognostic indicator for NPC patients.
Results of surgical treatment for squamous carcinoma of the lower alveolus: Segmental vs. marginal resection
Authors: Totsuka Yasunori , Usui Yasuhiro , Tei Kanchu , Kida Masataka , Mizukoshi Takanori , Notani Ken‐Ichi , Fukuda Hiroshi
Published: February 2007

The records of 53 patients treated surgically for squamous cell carcinoma of the lower alveolar ridge were reviewed and the results of segmental and marginal resections of the mandible were compared. Analysis of these 2 treatment modalities disclosed that marginal resection was effective in controlling lower gingival cancers, with and without apparent bone involvement, if erosive bone defects that did not extend beyond the inferior alveolar canal, or invasive bone defects confined to a superficial area of the alveolar bone, were detected radiologically.
Modified mandibular swing procedure for resection of carcinoma of the oropharynx
Authors: Sardi Armando , Walters P. J.
Published: February 2007

For most patients, the primary approach to carcinoma of the oropharynx has been with radiotherapy. We describe a modification of a mandibular swing procedure for resection of oropharyngeal lesions. This modification included a mandibulotomy that began in a staircase manner in the midline and extended laterally toward the ramus of the mandible to protect a long, fixed dental bridge. It also included the preservation of the mental nerve by unroofing the mandibular canal. No morbidity was associated with this procedure.
Branchio‐oto‐renal dysplasia associated with tetralogy of fallot
Authors: Daggilas Angelos , Antoniades Kostas , Palasis Sousan , Aidonis Athanasios
Published: February 2007

Branchio‐oto‐renal dysplasia in its full expression consists of external ear malformations, cervical fistulas or cysts, preauricular pits, hearing loss of conductive sensorineural or mixed type, and renal anomalies. The syndrome is inherited in an autosomal dominant mode. We present a sporadic case of BOR dysplasia associated with tetralogy of Fallot in a 30‐month‐old girl. The clinical aspects of the disease are discussed briefly.