bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of point mutations in the hprt gene of cancer patients treated with radioimmunoglobulin therapy
Authors: Skandalis A. , Curry J. , O'Neill J. P. , Nicklas J. A. , Albertini R. J. , Glickman B. W.
Published: February 2007

The mutagenic impact of various environmental and therapeutic agents can now be directly assayed in humans by the T‐lymphocyte cloning assay. We have previously reported that following radioimmu‐noglobulin therapy, cancer patients exhibited increased mutant frequency at the hprt locus and an increased yield of large intergenic deletions compared to unexposed controls. Here we report the results of the analysis of 26 independent hprt mutations in nine cancer patients who underwent radioimmunoglobulin therapy. The majority of mutations (52%) had lost exon sequences from the mRNA. The remaining mutations were 20% small deletions and frameshifts and 28% base substitutions. The type of mutations observed were similar to those seen in unexposed controls. The site distribution of the mutations, however, indicates that some sequence contexts may be more sensitive to radiation mutagenesis than others. © 1995 Wiley‐Liss, Inc.
Taurine and ellagic acid: Two differently‐acting natural antioxidants
Authors: Cozzi R. , Ricordy R. , Bartolini F. , Ramadori L. , Perticone P. , De Salvia R.
Published: February 2007

Naturally occurring antimutagenic compounds are extensively analyzed for their capacity to protect cells from induced damage. We selected two agents, taurine and ellagic acid, treated in the literature as antioxidants, but whose activity is insufficiently known. This paper reports on the ability of these agents to act against damage induced by mitomycin‐C and hydrogen peroxide in Chinese hamster ovary cells cultivated in vitro. Cytogenetic and cytofluorimetric analyses were performed. Ellagic acid proved to have more than one mechanism of action, probably as a scavenger of oxygen species produced by H2O2 treatment, and as a protector of the DNA double helix from alkylating agent injury. In our experimental conditions, taurine seems able to scavenge oxygen species. © 1995 Wiley‐Liss, Inc.
An examination of the potential “genotoxic” carcinogenicity of a biopesticide derived from the neem tree
Authors: Rosenkranz Herbert S. , Klopman Gilles
Published: February 2007

Structural analyses of azadirachtin, a promising biopesticide recently introduced into the United States, indicates that this natural product has the potential for acting as a “genotoxic” carcinogen. In view of the fact that genotoxic carcinogens are regarded as presenting a potential carcinogenic risk to humans, the present finding suggests that the possible metabolism of azadirachtin to DNA‐reactive products be evaluated experimentally. © 1995 Wiley‐Liss, Inc.
Methylglyoxal induces hprt mutation and DNA adducts in human T‐lymphocytes in vitro
Authors: Hou Sai‐Mei , Nori Peri , Fang Jia‐Long , Vaca Carlos E.
Published: February 2007

Methylglyoxal (MG) is a mutagen present in several foodstuffs, including coffee. We have used the 32P‐postlabelling method to measure MG‐deoxyguanosine adduct levels, and the T‐cell cloning technique, to study the frequency of hprt (hypoxanthine‐guanine phosphoribosyl transferase) mutant cells after treatment of human lymphocytes with MG in vitro. The mutant induction by single (18 hr) high‐dose (1.0–1.5 mM) treatment was comparable to that induced by repeated (3 × 48 hr) low‐dose (0.1–0.4 mM) treatment. The latter also correlated with the adduct levels measured in the same experiment. The relative cell survival measured by direct cloning after the final treatment agreed well with the growth curves monitored during the expression phase. Our results show that MG is capable of inducing hprt mutations as well as DNA adducts in human lymphocytes at doses with low cytotoxicity. However, significant adduct formation (two‐ to threefold) could be obtained only after the first exposure in cells subjected to a repeated treatment protocol, and the induced mutant frequency was low (two‐to fourfold over background). Thus, MG seems to be a comparatively weak mutagen in this system. © 1995 Wiley‐Liss, Inc.
Sister chromatid exchange in human lymphocytes induced by propoxur following plant activation by Vicia faba
Authors: Gómez‐Arroyo Sandra , Elena Calderón‐Segura M. , Villalobos‐Pietrini Rafael
Published: February 2007

Because the carbamate insecticide propoxur induced sister chromatid exchanges (SCE) in Vicia faba but was ineffective in producing SCE in lymphocytes in culture, it was hardly suspected that plant metabolism was involved. Experiments were conducted in which metabolic activation was afforded by Vicia faba roots, and SCE in human lymphocytes in vitro was used to assess cytogenetic damage. Several concentrations of propoxur (250, 500, 1, 000, 1, 500, and 2, 000 ppm) were applied for 4 hr to the roots of Vicia faba. Extracts prepared from these treatments were added to the lymphocyte cultures and a significant increase of SCE frequencies with a concentration‐response relationship could be detected. The lymphocyte proliferation kinetics and the proliferation rate index (PRI) were not affected (except in the highest concentration, of 2, 000 ppm). This general behavior was in agreement with the presence of an enzymatic system (SI0 fraction) in Vicia roots capable of metabolizing or activating the propoxur. With 2, 000 ppm, cell necrosis was produced in Vicia; therefore, this extract did not induce SCE in lymphocytes. However, lymphocyte proliferation kinetics were delayed and PRI was significantly decreased. Ethanol, a promutagen activated by this plant, was applied directly to the lymphocyte cultures as a positive control, and the response was negative. On the other hand, the extracts of roots treated with ethanol increased the SCE to more than twice that of the negative control, but the lymphocyte proliferation kinetics and PRI were not affected. © 1995 Wiley‐Liss, Inc.
Membrane fouling behavior during filtration of sludge supernatant
Authors: Yang Fenglin , Shi Baoqiang , Meng Fangang , Zhang and Hanmin
Published: February 2007

Colloidal particles and soluble matter in sludge supernatant are major membrane foulants during the operation of membrane bioreactors in wastewater treatment. The article discusses membrane fouling mechanisms during membrane filtration of sludge supernatant liquor. The influence of supernatant turbidity, transmembrane pressure, and crossflow velocity on membrane fouling was systematically investigated. The membrane fouling was characterized by Fourier transform infrared spectroscopy technique. The results showed that the high supernatant turbidity could result in severe membrane fouling because of the accumulation of colloidal particles and soluble matter on the membrane surfaces. High transmembrane pressure could lead to a high flux decline rate because of the formation of a dense cake layer. The crossflow velocity just had a slight influence on membrane fouling, as it was not larger than 0.12 m/s, However the membrane fouling decreased significantly as crossflow velocity increased to 0.24 m/s. The membrane fouling mechanisms of these operational conditions, including supernatant turbidity, transmembrane pressure, and crossflow velocity, were different from each other. Membrane fouling resistance can be predicted using a simple model based on supernatant turbidity, transmembrane pressure, and crossflow velocity. The major components of the foulants were proteins and polysaccharide materials. © 2007 American Institute of Chemical Engineers Environ Prog 26:86–93, 2007
Particle transport method for convection problems with reaction and diffusion
Authors: Shipilova O. , Haario H. , Smolianski A.
Published: February 2007

The paper is devoted to the further development of the particle transport method for the convection problems with diffusion and reaction. Here, the particle transport method for a convection–reaction problem is combined with an Eulerian finite‐element method for diffusion in the framework of the operator‐splitting approach. The technique possesses a special spatial adaptivity to resolve solution singularities possible due to convection and reaction terms. A monotone projection technique is used to transfer the solution of the convection–reaction subproblem from a moving set of particles onto a fixed grid to initialize the diffusion subproblem. The proposed approach exhibits good mass conservation and works with structured and unstructured meshes.

The performance of the presented algorithm is tested on one‐ and two‐dimensional benchmark problems. The numerical results confirm that the method demonstrates good accuracy for the convection‐dominated as well as for convection–diffusion problems. Copyright © 2007 John Wiley & Sons, Ltd.
High p21RAS expression levels correlate with chromosome 8 rearrangements in benign human mixed salivary gland tumors
Authors: Stenman Göran , Sandros Jens , Mark Joachim , Nordkvist Anders
Published: February 2007

The expression of RAS oncogenes in benign and malignant salivary gland tumors was studied by immunohistochemistry and by immunoblotting using monoclonal antibodies recognizing the HRAS and KRAS gene products. Twenty‐eight out of 29 benign pleomorphic adenomas overexpressed p21RAS, whereas only 12 out of 18 malignant salivary gland tumors expressed the p21 protein. The expression levels were also substantially higher in the adenomas than in the malignant tumors, indicating that RAS gene activation appears to be more frequent and of greater importance for benign than for malignant salivary gland tumors. Comparisons of the p21 expression levels with the karyotypes of the pleomorphic adenomas revealed a novel correlation between high p21 expression and chromosome 8 rearrangements. As a hypothesis, it is suggested that a novel gene located on the proximal long arm of chromosome 8, most likely at band q12, is involved in the regulation of RAS gene expression.
Frequency and extent of allelic loss in the short arm of chromosome 3 in nonsmall‐cell lung cancer
Authors: Rabbitts Pamela , Douglas Jenny , Daly Maria , Sundaresan Vasi , Fox Bernard , Haselton Philip , Wells Frank , Albertson Donna , Waters Jonathan , Bergh Jonas
Published: February 2007

DNA was prepared from tumour and normal tissue from 48 patients representing all common histological types of nonsmall‐cell lung cancer. Using eight DNA probes, which detect nine restriction enzyme fragment length polymorphisms (RFLP) on chromosome 3, we established that among the 44 informative patients 32 had lost alleles on the short arm of one of their copies of chromosome 3. Of these 32, at least 13 had also lost alleles on the long arm of chromosome 3, suggesting that the whole chromosome might be lost. For one patient, cytogenetic analysis indicated that the mechanism of allelic loss was reciprocal translocation followed by chromosomal loss of one of the reciprocal products. Two patients with allelic loss distal to the D3S3 locus (which maps to 3p13–14) retained heterozygosity at that locus. These results indicate that loss of alleles on the short arm of chromosome 3 is a common event in lung tumours of the nonsmall‐cell type, that this loss occurs by a variety of chromosomal mechanisms, and that the minimally deleted region is 3p13–14→3pter.
Homozygosity for 8pter→q22 in acute myeloblastic leukemia with t(8;21)(q22;q22)
Authors: Berger Roland
Published: February 2007

A case of acute nonlymphocytic leukemia with homozygosity for the chromosome segment 8pter→8q22 is reported. A t(8;21)(q22;q22) translocation was associated with duplication of the derivative chromosome 8q – and absence of the normal chromosome 8. These rearrangements also yielded hemizygosity for 8q22→qter. This case shows that acquired hemizygosity and homozygosity do exist in leukemia as in solid malignant tumors.
Premature chromosome condensation in childhood acute lymphoblastic leukaemia: Correlation of proliferative potential index in blood and marrow
Authors: Macleod Roderick A. F. , Hill Frank G. H. , Creasy Michael R. , Hulten Maj A.
Published: February 2007

The proliferative potential index (PPI), which is the proportion of all G1 cells which are in late G1, has been shown to reflect disease state in patients with acute leukaemia. We have determined PPI in paired blood and marrow samples from children with acute lymphoblastic leukaemia (ALL) at different stages of the disease, and found a close correlation between blood and marrow PPI irrespective of disease stage. Therefore blood PPI can replace marrow PPI for monitoring disease control in ALL.
Gene dosage effect in acquired monosomy 7: Distinct behaviour of β‐glucuronidase and phosphoserine phosphatase
Authors: Minelli Antonella , Piantanida Mauro , Maserati Emanuela , Campagnoli Elena , Pasquali Francesco , Danesino Cesare
Published: February 2007

Evidence for gene dosage effect for β‐glucuronidase (GUSB) and phosphoserine phosphatase (PSP), whose genes are mapped on chromosome 7, was searched in a group of 13 patients with myeloproliferative disorders and acquired monosomy 7. The monosomy 7 was the sole anomaly in nine patients and was associated with other chromosome changes in four. A group of 19 patients with similar diseases but with normal karyotype or with anomalies not involving chromosome 7 served as control. β‐galactosidase and arylsulphatase A, whose genes are not on chromosome 7, were tested as control enzymes. We obtained evidence for a gene dosage effect for GUSB, but not for PSP. When all cases with monosomy 7 were compared with controls, no dosage effect was observed for PSP, but when this group was split into two, according to the presence of anomalies additional to the monosomy 7, the values of activity in the group with additional anomalies were significantly lower than in the controls. Thus, in the case of PSP, the loss of one allele is not followed immediately by reduction in activity, and this could be due to the specific importance of PSP in nucleic acid metabolism. We postulate that some regulatory mechanisms are able to keep normal levels of PSP even in the presence of only one allele, and that they are overwhelmed only when additional chromosome changes are present. These changes tend to involve chromosomes carrying genes for enzymes involved in a metabolic pathway closely related to PSP functions, and only then is a gene dosage effect for PSP detectable.
Multiple methylation‐free islands flank a small breakpoint cluster region on 11p13 in the t(11;14)(p13;q11) translocation
Authors: Foroni Letizia , Boehm Thomas , Lampert Fritz , Kaneko Yasuhiko , Raimondi Susanna , Rabbitts Terence H.
Published: February 2007

The t(11;14)(p13;q11) translocation is one of the most frequent chromosomal abnormalities in T‐cell acute lymphoblastic leukemia (ALL). Ten different leukemias carrying this translocation have been analysed and all 10 breakpoints fall within a region of less than 25 kb on chromosome band 11p13. We have used PFGE and cosmid cloning to assess the presence of potential genes by analysing methylation‐free islands in the vicinity. Four methylation‐free islands, within 270 kb, flank the t(11;14)‐associated breakpoint cluster region (T‐ALLbcr), one occurring about 25 kb on the telomeric side and one about 100 kb on the centromeric side of the T‐ALLbcr. Evidence for eight further methylation‐free islands on both sides of the T‐ALLbcr region is also presented. Thus multiple methylation‐free islands exist on 11p13 flanking the t(11;14)(p13;q11) translocation‐associated breakpoint cluster region, representing multiple potential transcription units whose chromosomal environment is altered by chromosome translocation.
Karyotypic changes identified by HaeIII restriction endonuclease banding in a patient with M2 acute non‐lymphoblastic leukemia
Authors: Stuppia Liborio , Palka Giandomenico , Fioritoni Giuseppe , Calabrese Giuseppe , Franchi Paolo Guanciali , D'Arcangelo Luigi , Torlontano Glauco
Published: February 2007

A patient with acute non‐lymphoblastic leukemia, FAB type M2, showed a complex karyotype involving chromosomes 1 and 11. The breakpoints could not be exactly identified by GTG and QFQ banding. A subsequent analysis with AluI and HaeIII restriction enzyme staining allowed the detection of a translocation of the heterochromatic region of chromosome 1 to 11q21.
No evidence for loss of alleles at 11p in HBV negative hepatocellular carcinomas
Authors: Kiechle‐Schwarz Marion , Scherer Gerd , Kovacs Gyula
Published: February 2007

The aim of the present study was to determine whether loss of DNA sequences at the chromosome arm 11p, where presumed tumor suppressor genes are located, might occur in hepatocellular carcinomas (HCCs) of hepatitis B virus (HBV) negative patients. Normal liver and HCC genotypes were compared at 6 loci on 11p with 7 polymorphic probes detecting 10 restriction length polymorphisms (RFLPs). Each of the 8 paired normal‐tumor tissue samples was informative for at least three different loci on 11p13‐pter. None of them showed loss of constitutional heterozygosity for those markers. The retainment of 11p alleles suggests that mechanisms other than loss of tumor suppressor genes on 11p are involved in hepatocarcinogenesis of HBV negative patients.
Trisomy 12 is a consistent chromosomal aberration in benign ovarian tumors
Authors: Pejovic Tanja , Heim Sverre , Mandahl Nils , Elmfors Bengt , Flodérus Ulla‐Maria , Furgyik Stefan , Helm Góran , Willén Helena , Mitelman Felix
Published: February 2007

Clonal karyotypic abnormalities were detected in 7 of 42 cytogenetically analyzed benign ovarian tumors. An adenofibroma had –X and a mucinous cystadenoma had t(1;11)(q25;q23) as the sole abnormality. Trisomy 12 was found in the remaining five tumors. It was the only change in two fibromas and a serous cystadenoma; the fourth tumor, a mucinous cystadenoma, had one clone with + 12 and one with + 12 and + 10, and the fifth tumor, a fibrothecoma, had +4, +9, +12. The finding of trisomy 12 in five of seven karyotypically aberrant tumors suggests that this aberration characterizes a hitherto unrecognized cytogenetic subgroup of benign ovarian neoplasms.
RAS gene activation in acute myelogenous leukemia: Analysis by in vitro amplification and dna base sequence determination
Authors: Mane Shrikant M. , Meltzer Stephen J. , Gutheil John C. , Kapil Vikram , Lee Edward J. , Needleman Samuel W.
Published: February 2007

RAS protooncogene activation has been repeatedly demonstrated in neoplastic cell DNA from patients with AML. Despite the convincing demonstration that activating RAS gene point mutations are critical in model systems, their precise prevalence and importance in human cancers such as AML remain speculative. The technology for identifying RAS mutations has changed considerably in recent years. We examined a prospective cohort of 43 acute myeloid leukemia (AML) patients admitted to the University of Maryland Cancer Center for first and second exon mutations of NRAS and KRAS using PCR and DNA sequence analysis. Six (14%) 1st exon NRAS mutations were identified. No clinical or biologic parameter has yet been observed to segregate with RAS activation, although a larger study may be needed to demonstrate this.
New localizations of VH sequences by in situ hybridization with biotinylated probes
Authors: Cherif Dorra , Berger Roland
Published: February 2007

The chromosomal localization of genes of three VH families (VH1–3) was performed using in situ hybridization with biotinylated probes. Significantly strong signals were observed on chromosome 14, band 14q32, and on bands 16p11 and 15q11, although less frequently. Signal intensity and frequency were more important on chromosome 14 with all three probes, and on chromosome 16 with the VH2 and VH3 probes, while chromosome 15 was more marked than 16 with the VH1 probe. The localization of VH genes on chromosomes other than 14 suggests that several genes of the VH family had been simultaneously translocated in evolution and that the newly localized VH sequences may be pseudogenes.
Monosomy 12p in a radiation‐induced germ cell tumor
Authors: Cowan Janet M. , Beckett Michael A. , Tarbell Nancy J. , Weichselbaum Ralph R.
Published: February 2007

We report results of cytogenetic analysis of a cell line established from a radiation induced germ cell tumor. Tumors of this type are rare, and there is only one other report of chromosome analyses of solid tumors induced by radiotherapy (Cowan et al., 1990). The cells were grown for over a year, and harvested at passage 13. The karyotype was pseudodiploid, with several balanced translocations. Spontaneously occurring germ cell tumors are associated with i(12p). We did not observe an i(12p), but instead found monosomy of 12p and 7q22→q32.
High resolution mapping of consistent leiomyoma breakpoints in chromosomes 12 and 14 to 12q15 and 14q24.1
Authors: Pandis Nikos , Heim Sverre , Bardi Georgia , Mandahl Nils , Mitelman Felix
Published: February 2007

A substantial percentage of uterine leiomyomas are cytogenetically characterized by consistent, clonal chromosome abnormalities, including t(12;14)(q14–15;q23–24) and other rearrangements of 12q14–15 that occur without any visible 14q changes. The partly similar banding characteristics of these two regions have hitherto precluded exact mapping of the 12q and 14q breakpoints to any particular band, let alone their assignment to subbands. In the series of four myomas presented here, in which one tumor had inv(12q), two t(12;14), and one a three‐way t(7;12;14), we were able to achieve high resolution banding (550 band stage) of the rearranged chromosomes in several metaphases. This enabled us to assign a 12q breakpoint to 12q15 in all tumors and, in the three cases informative in this regard, the 14q breakpoint to 14q24.1. The more precise breakpoint mapping considerably narrows down the area that must be examined with molecular genetic methods in order to identify the gene loci that are rearranged in leiomyomas with 12q and 14q aberrations. It will also help determine to what extent leiomyoma rearrangements of 12q involve the same loci that are affected in 12q changes in other tumor types, e.g., in pleomorphic adenomas of the salivary gland, in lipomas, and in myxoid liposarcomas. At present it seems that the breakpoint in 12q may be cytogenetically identical in the three benign tumors, whereas it in myxoid liposarcomas appears to be more proximal.
Is the chromosome band 1p36 another hot‐spot for rearrangements in uterine leiomyoma?
Authors: Vanni Roberta , Cin Paola Dal , van den Berghe Herman
Published: February 2007

Two uterine leiomyomas showing involvement of bands 1p36 and 2p24 are reported. These rearrangements may indicate a new hot‐spot for chromosome changes in this neoplasia, 1p36, and confirm the existence of a specific subgroup in leiomyomas, t(1;2)(q36;p24).
Mapping of translocation breakpoints on the short arm of chromosome 19 in acute leukemias by in situ hybridization
Authors: Saltman David L. , Mellentin Julia D. , Smith Stephen D. , Cleary Michael L.
Published: February 2007

Non‐random translocations involving the short arm of chromosome 19 are frequently observed in acute leukemias. Recent studies have shown that the 19p13 genes E2A and LYL1, both of which encode helix‐loop‐helix proteins, lie at two different translocation breakpoints in acute lymphoblastic leukemias (ALL). The E2A gene is involved by the t(1;19)(q23;p13) in acute pre‐B‐cell leukemias and the LYL1 gene is structurally altered by a t(7;19)(q34;p13) in T‐cell ALL. To assess the role of these genes in other leukemia‐associated translocations we mapped their locations with respect to the t(11;19)(q23;p13) and t(4;19)(q21;p13) translocation breakpoints carried by T‐ALL cell lines SUP‐T13 and SUP‐T8a, respectively. In situ hybridization studies indicated that the E2A and LYL1 genes are physically distinct from the t(4;19) and t(11;19) breakpoints. Using these and other 19p13 translocation breakpoints as landmarks, we established a partial physical map of 19p: 19pter‐E2A‐INSR‐LYL1‐[t(4;19), t(11;19)]‐19cen. These data should help guide molecular studies to further characterize 19p13 breakpoints and mapping of genes in this chromosomal region.
1P13 is the most frequently involved band in structural chromosomal rearrangements in human breast cancer
Authors: Mitchell Erika L. D. , Santibanez‐Koref Mauro F.
Published: February 2007

Cytogenetic data on 14 breast carcinomas were examined to determine which chromosome arms and bands are preferentially involved in structural chromosome changes. Chromosome arms 17p, 16q, and 1p and band 1p13 were found to be significantly involved. A review of the world literature confirmed 1p as being the most frequently involved arm in structural chromosome changes in breast cancer and 1p13 as being the band most frequently involved in such changes. The two sets of results were pooled, and the analysis of 113 tumours revealed 229 of 304 bands to be involved, with 1p13 affected in 20% of the tumours.
Comparative cytogenetic analysis between cyclophosphamide‐sensitive and ‐resistant lines of acute myeloid leukemia in the lewis brown norway hybrid rat
Authors: Kearns William , Koelling Todd , Yeager Andrew
Published: February 2007

An animal model of acute myeloid leukemia (AML) has been developed in the Brown Norway (BN) rat and has successfully been introduced into the Lewis x BN F1 hybrid (LBN) and designated LBN AML. The original LBN AML is sensitive to the chemotherapeutic agent cyclophosphamide (CY). Recently, a CY‐resistant cell line of LBN AML has been established. To characterize this animal model of human leukemia better, we analyzed and compared the chromosomal makeup of both the CY‐sensitive and CY‐resistant LBN AML lines. The CY‐sensitive LBN AML cultures contained two cell lines—line 1 (88%):41, XX, –1, –2, –9,del(12)(q16),+der(1)t(1;?8)(p13;q31),+der(2)t(2;9)(p11;q11); and line 11 (12%): 41,XX,–1,–2,–9,del(12),del(20)(q13)+der(1)t(1;?8)(p13;q31),+der(2)t(2;9)(p11;q11). The recently developed CY‐resistant AML cells contained two cell lines—line 1 (88%): 41,XX,–1,–2,–9,del(3)(q36q42.1),del(4)(q42.2),?t(5;?)(q35;?),?t(8;?)(q24;?),del(12)(q16),+der (1)t(1;?8)(p13;q31),+der(2)t(2;9)(p11;q11); and line II (12%): 42,XX (probably represents host contamination). The new chromosomal aberrations in the CY‐resistant line 1 [del(3)(q36q42.1),del(4)(q42.2),?t(5;?)(q35;?), and ?t(8;?)(q24;?)] suggest a possible interrelationship between these secondary karyotypic abnormalities and acquisition of resistance to the chemotherapeutic agent.
Karyotypic evolution in B‐cell chronic lymphocytic leukaemia
Authors: Oscier David , Fitchett Margaret , Herbert Tony , Lambert Richard
Published: February 2007

Sequential cytogenetic studies were performed on a minimum of two and a maximum of nine occasions (mean 3.6) on the peripheral blood leucocytes of 112 patients with B‐CLL. On initial cytogenetic analysis, 58 had a normal karyotype and 64 had a clonal abnormality. Karyotypic evolution occurred in 18 patients (16%). There was no significant difference in the incidence of disease progression between patients with a stable karyotype and those who underwent karyotypic evolution. In only one patient was there a clear association between disease progression, a change in cell morphology and karyotypic evolution.
Rearrangement of 9p13 as the primary chromosomal aberration in adenoid cystic carcinoma of the respiratory tract
Authors: Higashi Koichiro , Jin Yuesheng , Johansson Maria , Heim Sverre , Mandahl Nils , Biörklund Anders , Wennerberg Johan , Hambraeus Göran , Johansson Leif , Mitelman Felix
Published: February 2007

Two adenoid cystic carcinomas, one of the nasal cavity, the other a bronchial tumor, were cytogenetically analyzed. The former had a t(6;9)(q21‐22;p13‐21) as the sole karyotypic abnormality. The latter had two related abnormal clones, resulting in the mosaic karyotype 46, XY, t(9;17)(p13;p13)/46, Y, t(X;6)(p22;q23), t(9;17)(p13;p13). The karyotypic profiles of the two cases, the only respiratory tract adenoid cystic carcinomas that have been cytogenetically characterized, differ little from those of previously reported adenoid cystic carcinomas of the major salivary glands, underscoring the fundamental biologic similarity among these tumors even when they develop from different structures and in different anatomical sites and organs. Because in the second case the t(9;17) obviously must have preceded the t(X;6), we conclude that both tumors had rearrangement of 9p13 as the primary cytogenetic change. The data thus add to the evidence that 6q changes are frequent, albeit at least sometimes secondary, aberrations in malignant salivary gland tumors. A subset of adenoid cystic carcinomas instead have rearrangement of 9p as the primary, and presumably pathogenetically essential, abnormality.
A chromosome 12 coding region is juxtaposed to the MYC protooncogene locus in a t(8; 12)(q24;q22) translocation in a case of B‐cell chronic lymphocytic leukemia
Authors: Rimokh Ruth , Rouault Jean‐Pierre , Wahbi Kamal , Gadoux Mylène , Lafage Marina , Archimbaud Eric , Charrin Christiane , Gentilhomme Odile , Germain Daniel , Samarut Jacques , Magaud Jean‐Pierre
Published: February 2007

We performed molecular cloning and sequencing of the breakpoints of a new chromosomal translocation involving the MYC protooncogene locus. This secondary t(8; 12)(q24;q22) was associated with a primary t( I I; 14)(q I 3;q32) translocation in a case of B‐cell chronic lymphocytic leukemia (CLL) in blastic transformation. In this leukemia, Northern blot and nuclease analyses SI showed that MYC was strongly expressed with initiation of the transcription at both the 5′ and 3′ promoters as observed in Burkitt's lymphomas; no coding change was observed in MYC putative regulatory sequences. The breakpoint on chromosome 8 mapped to the 3′ end of the MYC locus, in a region containing a potential Z‐DNA tract, and where we identified two DNase I hypersensitive sites. A rearranged MYC gene fragment was cloned and shown to contain chromosome 12 information by Southern blot analysis and by in situ hybridization. A genomic probe subcloned from the isolated region of the chromosome 12 recognized a 1.8 kb transcript in virtually all the tissues tested but a preferential expression of this new gene, which we termed BTGI (for B‐cell translocation gene I) was observed in the CLL cells and in tissues of lymphoid origin. This chromosome 12 coding sequence is conserved in evolution and a transcript of similar size is present in murine tissues.
Translocations t(X;7) and t(7; 14) in a synovial sarcoma
Authors: Verhest Alain , Limon Janusz , Mrózek Krzysztof , Nedoszytko Boguslaw
Published: February 2007

Cytogenetic analysis of a metastatic biphasic synovial sarcoma showed two structural abnormalities: t(X;7)(q 11 or 12;q32) and t(7;14)(q22;q11.2). This is the first report of a synovial sarcoma without the involvement of either Xp11 or 18q11.
Abnormalities of 2q: A common genetic link between rhabdomyosarcoma and hepatoblastoma?
Authors: Rodriguez Eduardo , Reuter Victor E. , Mies Carolyn , Bosl George J. , Chaganti R. S. K.
Published: February 2007

Cytogenetic and restriction fragment length polymorphism (RFLP) analyses were performed on a mediastinal germ cell tumor comprising distinct teratoma and embryonal rhabdomyosarcoma components in a 31‐year‐old male and a hepatoblastoma in a 2 month‐old male child. Clonal relationship between the teratoma and rhabdomyosarcoma of the germ cell tumor was established by the presence in both of i(12p), the characteristic marker of germ cell tumors. Both the rhabdomyosarcoma component of the mediastinal germ cell tumor and the hepatoblastoma exhibited rearrangements of 2q. These data suggest that malignant differentiation of a teratoma is accompanied by the development of chromosome abnormalities specific for the transformed histology and further suggest that 2q abnormalities may be the common genetic link in the development of the two histologically unrelated tumor types, embryonal rhabdomyosarcoma and hepatoblastoma.
DNA discontinuities in the domain of amplified human MYC oncogenes
Authors: Bianchi Néstor O. , Bianchi Martha S. , Kere Juha
Published: February 2007

COLO320DM and COLO320HSR are cell lines derived from a human colon carcinoma, Both lines have an amplification of the MYC oncogene: COLO320DM in the form of double minute chromosomes, COLO320HSR as a large marker chromosome with homogeneously staining regions. We have used pulsed field gel electrophoresis (PFGE) to analyze undigested DNA from both COLO320 cell lines. Upon blotting and hybridization with a MYC probe, the autoradiograms showed the existence of discontinuities in the amplified DNA domains. Additional evidence indicating a preferential concentration of DNA breaks in the region containing the MYC amplicons was obtained with the alkaline unwinding technique. We propose that amplicons are connected by hairpin formation or Hoogsteen pairing between free DNA ends.
Transcriptional deregulation of myc inlgH/myc 6;7 translocation carrying rat immunocytomas
Authors: Axelson Håkan , Pear Warren S. , Panda Chinmay Kumar , Bazin Herve' , Klein George , Sümegi Janos
Published: February 2007

We have previously shown that the reciprocal translocation t(6;7) associated with the spontaneous immunocytoma of the Louvain rat (RIC) leads to the juxtaposition of myc to the lgH cluster. In 10 of 14 tumors investigated the breakpoints on the myc carrying chromosome were clustered in a 1.5 kb region 5′ of the intact gene, proximal to the myc promoters. In this paper we describe the effect of the translocation on myc transcription in the RIC system. Run‐on analysis showed transcriptional attenuation in the normal rat myc gene, similar to the situation in mice and humans. The attenuation was almost completely abrogated in the three immunocytomas studied. Sequence analysis of two tumors failed to reveal any structural changes within exon I, as found by others in Burkitt's lymphoma. We also show that the transcriptional initiation of myc mRNA is changed in the RICs. In an established line of rat fibroblasts (Rat‐2), the more distal myc promoter (P2) is the preferred site of initiation. In RIC, however, only 30% of transcripts were initiated from P2. We found that 40% of the transcripts were initiated from PI and 30% from a novel promoter, designated PI a, located between PI and P2.
Trisomy 7 in Short‐Term Cultures of Colorectal Adenocarcinomas
Authors: Bardi Georgia , Johansson Bertil , Pandis Nikos , Heim Sverre , Mandahl Nils , Andrén‐Sandberg Åke , Hägerstrand Inga , Mitelman Felix
Published: February 2007

Cytogenetic analysis of short‐term cultures from six adenocarcinomas of the colon revealed trisomy 7 as a recurrent clonal chromosomal abnormality. In three tumors, +7 was the sole change. In the fourth carcinoma, two aberrant clones with simple numerical aberrations were detected; one with +7 and one with +3. Tumors 5 and 6 both displayed two completely different abnormal clones; one had numerous numerical and structural abnormalities and thus was undoubtedly representative of the cancer parenchyma, and the other had only +7. The karyotypic differences between the coexisting clones in the latter two cases seem to argue against an evolutionary scenario in which the karyotypically more complex clones have evolved from the clones carrying trisomy 7 only. Furthermore, in tumor 6 the metaphases with trisomy 7 were found in colonies of fibroblast‐like cells whereas those with a large number of abnormalities grew in colonies of epithelial‐like cells. The combined results indicate that mitoses with trisomy 7 as the sole chromosomal change do not represent the neoplastic parenchyma of colorectal adenocarcinomas.
Molecular and cytogenetic analysis of chromosomal arms 2q and 13q in alveolar rhabdomyosarcoma
Authors: Barr Frederic G. , Biegel Jaclyn A. , Sellinger Beatrice , Womer Richard B. , Emanuel Beverly S.
Published: February 2007

We present cytogenetic and molecular genetic analyses of two cases of alveolar rhabdomyosarcoma. The characteristic translocation between chromosomes 2 and 13, t(2;13)(q35;q14), has been identified in both cases. Using cell lines derived from these tumor specimens, we have performed Southern blot analysis to investigate the possibility of rearrangement of 14 candidate genes mapping to the relevant regions of 2q and 13q. These candidate genes can be divided into 5 groups: signal transduction proteins (RBI, inhibin α, FLTI, and HOX4B), muscle‐specific products [myosin light chain, desmin, and nicotinic cholinergic receptor subunits γ and δ (CHRNG and CHRND)], extracellular matrix proteins (collagen type VI α3 chain, elastin, and fibronectin), transformation‐associated products (intestinal alkaline phosphatase and L‐plastin), and other genes (esterase D). Conventional gel electrophoresis followed by Southern blot analysis indicated no evidence of rearrangement within or near these genes except for a rearrangement in the CHRNG‐CHRND locus, which occurred only in a subpopulation of the late recurrence tumor cells of one patient. In addition, we employed pulsed‐field gel electrophoresis—Southern blot analysis to demonstrate the absence of detectable rearrangements within a larger region around each of these genes.
t(18;22)(q21;q11) with rearrangement of BCL2 as a possible secondary change in a lymphocytic lymphoma
Authors: Leroux Dominique , Hillion Josette , Monteil Michele , Marc'hadour Francois Le , Jacob Marie‐Christine , Sotto Jean Jacques , Larsen Christian Jacques
Published: February 2007

We report a lymphocytic lymphoma showing a combination of two characteristic neoplasia‐associated chromosomal changes: trisomy 12, commonly observed in chronic lymphocytic leukemia and lymphocytic lymphoma, and t(18;22)(q21;q11), a variant form of the t( 14; 18)(q32;q21) found in most follicular lymphomas. Southern blot analysis was performed using probes for the 5′ end of the BCL2 gene (18q21) and for the JX as well as CX immunoglobulin genes (22q11). With these two probes, a unique rearranged fragment was detected. Thus the t(18;22)(q21;q11) can be considered as a variant translocation of t( 14; 18)(q32;q21). The karyotypic analysis supports the assumption that in our case trisomy 12 occurred first, and t(18;22) appeared during tumor progression as part of the clonal evolution. This is at variance with the typical t( 14; 18), which has never been found to occur as a secondary change.
Specific chromosome change associated with acquisition in vivo of tumorigenicity in carcinogen‐induced rat urinary bladder carcinoma cells
Authors: Debiec‐Rychter Maria , Azuma Masayuki , Zukowski Kim , Oyasu Ryoichi , Wang Ching Y.
Published: February 2007

The correlation between chromosomal changes and tumorigenic potential of rat bladder epithelial cells was investigated. Seven cell lines were established from neoplastic urothelial cells derived from heterotopically transplanted rat bladders treated with topical application of one of two carcinogens, N‐methyl‐N‐nitrosourea (MNU) or N‐hydroxy‐N‐glucuronosyl‐2‐aminofluorene. Loss of the short arm of chromosome 3 was demonstrated in three of four lines tumorigenic in the nude mouse, but in none of three nontumorigenic lines. One of the three nontumorigenic cell lines (D44c) was treated further in vitro with MNU. All six tumorigenic, but none of the four nontumorigenic, morphologically altered cell lines derived from D44c demonstrated loss of the short arm of chromosome 3. These results suggest that chromosome 3 alterations may be associated with the tumorigenicity of carcinogen‐induced rat bladder epithelial cells.
Trisomy 2 and 20 in two hepatoblastomas
Authors: Soukup Shirley W. , Lampkin Beatrice L.
Published: February 2007

Cytogenetic analysis of two pediatric hepatoblastomas is presented, comparing results in primary tumor samples, nude mouse xenographs, and lung metastases in one case. Both tumors had trisomy 2 and 20 in the primary tumors, along with other structural abnormalities. In subsequent passages/metastases, both tumors showed structural changes in one chromosome 2, resulting in partial trisomy 2q, along with structural changes of other chromosomes. Partial trisomy 1 q was also common to both tumors in late stages. Results are compared to those of embryonal rhabdomyosarcoma, where trisomy 2 has also been noted.
Trisomy 8 as the only chromosome change in an epithelioid smooth muscle tumor
Authors: Cin Paola Dal , De Wever Ivo , Aerts Raymond , Van Damme Boudewijn , Van Den Berghe Herman
Published: February 2007

Epithelioid smooth muscle tumor is a rare low grade malignancy that usually occurs in the gastrointestinal tract. No chromosome studies of this tumor have been reported so far. We found trisomy 8 as the sole chromosome anomaly in a large hepatic epithelioid smooth muscle tumor.
Is t(6;20)(p21;q13) a characteristic chromosome change in endometrial polyps?
Authors: Speleman Frank , Cin Paola Dal , Van Roy Nadine , Van Marck Eric , Buytaert Philip , Van Den Berghe Herman , Leroy Jules G.
Published: February 2007

Cytogenetic analysis of an endometrial polyp showed the presence of a t(6;20)(p21;q13) together with an ins(16;1)(q22;q32q42). Since a 6;20‐translocation has been previously found in another endometrial polyp, we think that t(6;20)(p21;q13) may be a characteristic chromosomal change in endometrial polyps.
Cytogenetic Studies in Acute Promyelocytic Leukemia: A Survey of Secondary Chromosomal Abnormalities
Authors: Berger Roland , Coniat Maryvonne Le , Derré Josette , Vecchione Danièle , Jonveaux Philippe
Published: February 2007

A series of 105 patients with acute promyelocytic leukemia (APL) has been cytogenetically investigated at the Department of Hematology of the Saint‐Louis Hospital (Paris) between 1977 and 1990. Sixty‐two patients were examined at diagnosis, 32 in relapse, and 11 both at diagnosis and in relapse. The typical t( 15; 17)(q22;q 12) or variants of this translocation were observed in all but four patients. The t(15;17) was the only change in 47 cases at diagnosis and in 21 examined in relapse. The most frequent secondary change was trisomy 8 (17% at diagnosis). More or less complex chromosomal abnormalities in addition to t(15;17) were present in six patients at diagnosis, and in 17 patients in relapse. Rearrangements of 2q35‐q37 and del(11p) were observed only in relapse and may thus be nonrandom secondary changes. Cytogenetic studies performed on 19 patients treated with all‐trans retinoic acid did not indicate that this treatment induces chromosomal abnormalities.
Murine Radiation Myeloid Leukaemogenesis: A Possible Role for Radiation‐Sensitive Sites on Chromosome 2
Authors: Breckon George , Papworth David , Cox Roger
Published: February 2007

There is a paucity of informative data on the potentially important role of specific sites of chromosomal instability in oncogenic processes. Chromosome 2 deletions and rearrangements are known to characterise radiation‐induced acute myeloid leukae mia in the mouse. Here we statistically establish a concordance between chromosome 2 breakpoint clusters in these leukaemias and chromosome 2 rearrangements carried at a high in vivo frequency by progeny of irradiated haemopoietic cells. Mechanisms of radiation myeloid leukaemogenesis are discussed with respect to multiple radiation‐sensitive sites encoded on chromosome 2 and the possible influence of genomic imprinting on inductive processes.
Multiple DNA Rearrangements in the BCL2 Region in a Patient With Follicular Lymphoma
Authors: Lundgren Erik , Roos Göran , Nordenson Ingrid , Wahlin Anders , Lind Jack
Published: February 2007

A 39‐year‐old male with follicular non‐Hodgkin's lymphoma was repeatedly studied with respect to DNA rearrangements with the two probes pFL‐1 and pFL‐2, representing two segments of chromosome 18. The oncogene 6CL2, detected by pFL‐1, was as expected translocated to the J region of the immunoglobulin locus. The standard BCL2 translocation was found in three samples, one obtained at diagnosis, one ten months later, and one after 5 years. Another translocation was found with the probe pFL‐2 hybridizing with a region located about 20 kb 3' from BCL2. This latter rearrangement was found only in the first biopsy, which was obtained at the time of diagnosis, but not in the two later samples, when the morphology of the lymphoma was unchanged. No cytotoxic therapy had been given in the interval from diagnosis to disappearance of the latter rearrangement. Thus, one of the observed translocations (pFL‐2) was detected only in the first biopsy, while the other (pFL‐1) was a clonal marker in all three biopsies. The finding suggests that clonal evolution does not necessarily mean clinical progression.
Clear Cell Sarcoma with t( 12;22) (q13–14;q12)
Authors: Peulve Pascal , Michot Chantal , Vannier Jean‐Pierre , Tron Philippe , Hemet Jacques
Published: February 2007

Karyotypic analysis of a clear cell sarcoma revealed a translocation t(12;22) (q13–14;q12) as a primary chromosomal change. This case is the third clear cell sarcoma cytogenetically analyzed; the two previously reported cases had t( 12;22)(p 11;p 11), and a complex karyotype with trisomy 22, respectively.
Cytogenetic Findings in Aneurysmal Bone Cysts
Authors: Pfeifer F. Michael , Bridge Julia A. , Neff James R. , Mouron Barbara J.
Published: February 2007

Cytogenetic analysis was performed on samples from ten patients diagnosed with aneurysmal bone cyst. Six of the patients were male and four were female, with ages ranging from 7 to 24 years. Results were obtained in eight of the cases; all were karyotypically normal.
Consistent Chromosome Abnormalities in Squamous Cell Carcinoma of the Vulva
Authors: Worsham Maria J. , Van Dyke Daniel L. , Grenman Seija E. , Grenman Reidar , Hopkins Michael P. , Roberts James A. , Gasser Kathleen M. , Schwartz Donald R. , Carey Thomas E.
Published: February 2007

Six squamous cell carcinomas of the vulva (SCV) were karyotyped in short‐term culture and in early passages as established cell lines. Each tumor was cytogenetically distinct, contained multiple chromosome rearrangements, and was karyotypically stable in culture. Heterogeneity within individual tumors was manifested by the presence of more than one clonal population, but the clones within each tumor were closely related to one another. Seven consistent chromosome abnormalities found in five of the six tumors were: losses of 3p 14‐cen, 8pter‐p 11, 22q 13.1 ‐q 13.2, and the short arm of the inactive X; chromosome gains involving 3q25‐qter and 11 q21; and rearrangement breakpoints at 5cen‐q 12. Ten additional chromosome changes were observed in four of the six SCVs, and together, 22 changes occurred in at least three of the tumors. Two specific losses, 10q23‐q25 and 18q22‐q23, were present in all four tumors that exhibited biologically aggressive behavior in vivo, but these losses were not found in the tumors of the two long‐term survivors. These findings indicate that: 1) SCVs are genetically complex, but homogeneous; 2) loss of 18q22‐q23 and loss of 10q23‐q25 may be associated with a poor prognosis; and 3) development and progression of SCV appear to result from cumulative effects of altered gene dosage at multiple, consistent loci.