bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trisomy 7 in nonneoplastic cells
Authors: Johansson Bertil , Heim Sverre , Mandahl Nils , Mertens Fredrik , Mitelman Felix 
Published: February 2007

AbstractThe somatic mutation theory of tumorigenesis states that mutations are necessary for tumor development. On the other hand, acquired, clonal chromosomal alterations are occasionally detected in otherwise normal, nonneoplastic cells—for example, loss of sex chromosomes occurs in bone marrow cells and lymphocytes in elderly individuals—and it is therefore evident that not all mutations are by themselves sufficient for neoplasia to occur. Thus, the finding of an acquired, clonal chromosomal abnormality does not constitute proof that a lesion is neoplastic. Trisomy 7 has, as the sole clonal chromosomal aberration, been reported in a wide variety of epithelial tumor types but also in some mesenchymal and neurogenic neoplasms. It has been suggested to be a primary, i.e., tumor‐initiating, abnormality in tumors of the bladder, brain, colon, kidney, lung, ovary, prostate, and thyroid. But data from cytogenetic studies of solid tumors, macroscopically normal tissue in the proximity of solid tumors, and nonneoplastic lesions now question the importance of a solitary +7 as a neoplasia‐associated change. Most solid tumors in which trisomy 7 has been found as the sole change in one clone have also displayed other, cytogenetically unrelated, clones with complex karyotypic abnormalities. Such karyotypic differences among coexisting clones could indicate that the neoplasm is polyclonal, that the cytogenetically disparate clones have emerged during tumor progression from one original clone carrying submicroscopic genomic changes only, or that the clone with +7 does not represent the tumor parenchyma. The latter interpretation is supported by the finding of cells with trisomy 7 in macroscopically normal tissue outside tumors of the brain, kidney, and lung. A seemingly decisive argument against the belief that the finding of an acquired, clonal +7 proves that a neoplasm exists is the detection of clones with an extra copy of chromosome 7 in several nonneoplastic lesions and tissues, such as atherosclerotic plaques, chorionic villi, chronic pyelonephritis, Dupuytren's contracture, focal steatosis of the liver, Peyronie's disease, and rheumatoid synovitis. That the abnormality arises in vivo has been shown by in situ hybridization with chromosome 7 specific probes; +7 is no in vitro artifact. It is unknown in which cell type the trisomy occurs; some data from colon adenomas favor epithelial cells, whereas data from kidney tumors and colon carcinomas suggest that the +7 arises in cells of the immune system. This question may possibly be resolved by obtaining a pure cell line with trisomy 7 cells only, to be characterized further by immunologic and morphologic methods. Another line of investigation might be to search for clonal chromosomal abnormalities in nonneoplastic tissues in other species. Finally, it remains to be elucidated whether +7 is a neutral genome mutation or whether it confers a selective advantage upon the cell. © 1993 Wiley‐Liss, Inc.
Amplified region of chromosome band 11q13 in breast and squamous cell carcinomas encompasses three CpG islands telomeric of FGF3, including the expressed gene EMS1
Authors: Brookes Sharon , Lammie G. Alistair , Schuuring Ed , De Boer Carla , Michalides Rob , Dickson Clive , Peters Gordon 
Published: February 2007

AbstractDNA markers that map within the karyotypically defined band q13 on human chromosome 11 are amplified in a subset of mammary and squamous cell carcinomas. It is assumed that the amplified DNA includes a critical gene (or genes) whose overexpression provides a selective force in the development of the tumor. To help identify such genes, we have begun to construct a physical map of CpG islands in the region, making use of a squamous cell carcinoma cell line (UMSCC2) in which the 11q13 region is amplified 11‐fold. We previously described the proximal end of this amplicon and the order of markers extending ∼800 kb centromeric of the FGF3 locus (formerly INT2). We now report the use of chromosome jumping techniques to define additional CpG islands that lie distal to FGF3. These map within the amplified region in UMSCC2 cells and the most telomeric corresponds to the EMS1 gene. The data imply that the amplified DNA in UMSCC2 cells extends for over 1,500 kb and includes at least 7 potential genes. EMS1 and CCND1 (formerly PRAD1), the best candidates for the key gene on the 11q13 amplicon, are ≥800 kb apart. © 1993 Wiley‐Liss, Inc.
The human NME2 gene lies within 18kb of NME1 in chromosome 17
Authors: Chandrasekharappa Settara C. , Gross Laura A. , King Stephanie E. , Collins Francis S. 
Published: February 2007

AbstractThe NME1 gene, localized to human chromosome 17 at q22, shows reduced expression in tumors of high metastatic potential. A homologous gene, NME2, with similar reduced expression in breast carcinoma, has recently been reported. We have isolated and characterized five yeast artificial chromosome (YAC) clones and three cosmid clones that contain both genes, demonstrating that the NME2 gene is also located on chromosome 17 and is separated by not more than 18 kb from the NME1 gene. The two putative tumor suppressor genes, encoding the two polypeptide chains of nucleoside diphosphate (NDP) kinase, are thus quite close to each other on chromosome 17, indicating that they may well have arisen by a tandem duplication. Both genes now appear to be excluded as candidates for the early‐onset breast cancer (BRCA1) locus. © 1993 Wiley‐Liss, Inc.
Characterization of human bone marrow‐derived closed circular DNA clones
Authors: Lou Zhuangwei , Kastury Kumar , Crilley Pamela , Lasota Jerzy , Druck Teresa , Croce Carlo M. , Huebner Kay 
Published: February 2007

AbstractBecause of interest in mechanisms of recombination involved in chromosomal deletions in neoplastic disease, and their relation to possible rearrangements in normal tissues, we are studying circular DNA molecules from human tissue with a long‐term goal of investigating them as possible by‐products of physiologically relevant intrachromosomal recombination events. Covalently closed circular (ccc) DNA from human bone marrow was cloned in bacteriophage vectors, and fourteen clones chosen randomly from the cccDNA‐derived library were characterized. Five clones originated from chromosome‐specific centromeric α‐satellite DNA; two clones carried highly repetitive sequences probably derived from interspersed repetitive elements; six clones were derived from single‐copy chromosome‐specific sequences which detected homologous rodent sequences; and one clone (EPM10) was derived from a small chromosome 11‐specific sequence family which localized to chromosome regions 11cen and 11q14. Oligonucleotide primers derived from the cccDNA clones were used in polymerase chain reaction studies to show that (1) the EPM10 clone carried the circular junction, (2) several of the single‐copy products could be detected in three different bone marrow cccDNA preparations, and (3) the Alu‐PCR profile for bone marrow cccDNA showed distinct bands which were similar in four bone marrow cccDNA preparations. © 1993 Wiley‐Liss, Inc.
Pericentric intrachromosomal insertion responsible for recurrence of del(11)(p13p14) in a family
Authors: Henry Isabelle , Hoovers Jan , Barichard Fernande , Berthéas Marie‐Françoise , Puech Anne , Prieur Fabienne , Gessler Manfred , Bruns Gail , Mannens Marcel , Junien Claudine 
Published: February 2007

AbstractThe combined use of qualitative and quantitative analysis of 11p13 polymorphic markers together with chromosomal in situ suppression hybridization (CISS) with biotin labeled probes mapping to 11p allowed us to characterize a complex rearrangement segregating in a family. We detected a pericentric intrachromosomal insertion responsible for recurrence of del(11)(p13p14) in the family: an insertion of band 11p13‐p14 carrying the genes for predisposition to Wilms' tumor, WTI, and for aniridia, AN2, into the long arm of chromosome 11 in 11q13‐q14. Asymptomatic balanced carriers were observed over three generations. Classical cytogenetics had failed to detect this anomaly in the balanced carriers, who were first considered to be somatic mosaics for del(11)(p13). Two of these women gave birth to children carrying a deleted chromosome 11, most likely resulting from the loss of the 11p13 band inserted in 11q. Although in both cases the deletion encompassed exactly the same maternally inherited markers, there was a wide variation in clinical expression. One child, with the karyotype 46,XY,del(11)(p13p14), presented the full‐blown WAGR syndrome with aniridia, mental retardation, Wilms' tumor, and pseudohermaphroditism, but also had proteinuria and glomerular sclerosis reminiscent of Drash syndrome. In contrast, the other one, a girl with the karyotype 46,XX,del(11)(p13), only had aniridia. Although a specific set of mutational sites has been observed in Drash patients, these findings suggest that the loss of one copy of the WTI gene can result in similar genital and kidney abnormalities. © 1993 Wiley‐Liss, Inc.
Characterization of two 11q23.3–11q24 deletions and mapping of associated anonymous DNA markers
Authors: Sanford Janet P. , Sait Sheila N. J. , Pan Li , Nowak Norma J. , Gill Heidi J. , le Beau Michelle M. , Diaz Manuel O. , Zabel Bernhard , Shows Thomas B. 
Published: February 2007

AbstractTranslocations in bands 11q23.3–11q24 are associated with several human cancers, including acute lymphoid and acute myeloid leukemias (AML) and Ewing's sarcoma. We have characterized two independent deletions in this region, one derived from a patient with AML who previously had a T‐cell lymphoma, and another from a Wilms' tumor patient. Cytogenetic analysis of the ML‐2 cell line established from the malignant cells of the AML patient indicated that one chromosome 11 homolog had an interstitial deletion, del(11) (q23q24), and the remaining homolog was involved in a recurring translocation, t(6;11) (q27;q23). According to karyotype analysis on the Wilms' tumor patient (EH), one chromosome 11 was normal and the other carried an interstitial deletion at 11q23.3–11q25. Somatic cell hybrids segregating the EH deletion (EHR4) and the ML‐2 deletion (MLR4) have been isolated. The EH deletion is distal to the MLL probe recently associated with 11q23.3 leukemia breakpoints (Ziemin‐van der Poel et al.: Proc Natl Acad Sci USA 88:10735–10739, 1991). The ML‐2 deletion could involve the MLL gene at a point distal to other breakpoints within MLL Both deletions include the Ewing's sarcoma breakpoint at 11q24.1. By Southern blot analysis we identified three anonymous DNA markers (D11S272, D11S273, and D11S219) and the ETS1 oncogene, which map within each deleted region. These markers are conserved based on zoo blot analysis, and they are valuable for physical mapping and genetic characterization of a region that may code for gene products associated with growth control and tumor suppression in a variety of cancers. © 1993 Wiley‐Liss, Inc.
Deletion mapping of the short arm of chromosome 8 in non‐small cell lung carcinoma
Authors: Ohata Hiroyuki , Emi Mitsuru , Fujiwara Yoshiyuki , Higashino Kazuya , Nakagawa Ken , Futagami Reiko , Tsuchiya Eiju , Nakamura Yusuke 
Published: February 2007

AbstractFrequent losses of heterozygosity observed at several chromosomal loci in primary lung cancers have indicated the existence of several tumor suppressor genes associated with this type of cancer. We have examined loss of heterozygosity on chromosomal arm 8p in 49 cases of non‐small cell lung carcinoma, using 14 restriction fragment length polymorphism markers. Of 42 cases informative with at least one marker, 21 showed allelic loss, including 15 of 32 adenocarcinomas and 5 of 9 squamous cell carcinomas. The frequency of allelic loss on 8p was similar at all clinical stages. Deletion mapping defined a single common region of deletion in these tumors within an 8 cM interval at 8p21.3–p22 flanked by the loci defined by cMSR‐32 and cC18–245. © 1993 Wiley‐Liss, Inc.
Homozygous inactivation of WTI in a Wilms' tumor associated with the WAGR syndrome
Authors: Gessler Manfred , König Anja , Moore Jay , Qualman Steven , Arden Karen , Cavenee Webster , Bruns Gail 
Published: February 2007

AbstractWilms' tumor is a childhood nephroblastoma that is postulated to arise through the inactivation of a tumor suppressor gene by a two‐hit mechanism. A candidate 11p13 Wilms' tumor gene, WTI, has been cloned and shown to encode a zinc finger protein. Patients with the WAGR syndrome (Wilms' tumor, aniridia, genitourinary abnormalities, and mental retardation) have a high risk of developing Wilms' tumor and they carry constitutional deletions of one chromosome 11 allele encompassing the WTI gene. Analysis of the remaining WTI allele in a Wilms' tumor from a WAGR patient revealed the deletion of a single nucleotide in exon 7. This mutation likely played a key role in tumor formation, as it prevents translation of the DNA‐binding zinc finger domain that is essential for the function of the WTI polypeptide as a transcriptional regulator. © 1993 Wiley‐Liss, Inc.
FLT4 Receptor Tyrosine Kinase Gene Mapping to Chromosome Band 5q35 in Relation to the t(2;5), t(5;6), and t(3;5) Translocations
Authors: Armstrong Elina , Kastury Kumar , Aprelikova Olga , Bullrich Florencia , Nezelof Christian , Gogusev Jean , Wasmuth John J. , Alitalo Kari , Morris Steven , Huebner Kay 
Published: February 2007

AbstractFLT4 is a recently cloned receptor tyrosine kinase cDNA, which is characterized by seven immunoglobulin‐like loops in its extracellular domain. We have previously mapped the FLT4 gene to chromosome segment 5q33‐qter using somatic cell hybrids. Here we have refined the localization to band 5q35 by fluorescence in situ hybridization and show that the gene is translocated to chromosomes 2 and 6 in the t(2;5)(p23;q35) and t(5;6)(q35;p21) translocations, respectively, of Ki‐1‐positive lymphomas, as well as to chromosome 3 in the t(3;5)(q25.1;q34) translocation, which is occasionally found in myelodysplastic syndromes and acute myeloid leukemia. No evidence was obtained for a rearrangement or deregulation of the translocated FLT4 gene. We further show that abundant FLT4 mRNA expression occurs only in erythroid and megakaryoblastoid cell lines among nine leukemia cell lines studied. © 1993 Wiley‐Liss, Inc.
Deletion mapping of the long arm of chromosome 10 in glioblastoma multiforme
Authors: Fults Dan , Pedone Carolyn 
Published: February 2007

AbstractCytogenetic and restriction fragment length polymorphism (RFLP) studies have shown that loss of one entire copy of chromosome 10 is a common genetic event in glioblastoma multiforme, the most malignant glial brain tumor in humans. In a search for submicroscopic deletions, we carried out an RFLP analysis using markers that had been mapped accurately on chromosome 10 by genetic linkage analysis. We studied 30 patients of whom 15 had loss of heterozygosity (LOH) at one or more loci. In seven cases, LOH was found at every informative locus, whereas in two cases extensive deletions were observed involving both the short and long arms. In six other patients, LOH was confined to a portion of the long arm. The smallest region of overlap among these latter six deletions was flanked by markers D10S12 proximally and D10S6 distally, a 33.4 centimorgan region that maps physically near the telomere (q25.1‐qter). This region will serve as an important target for future mapping experiments designed to identify a tumor suppressor gene implicated in this lethal form of human cancer. Genes Chrom Cancer 7:173–177 (1993). © 1993 Wiley‐Liss, Inc.
Ovarian germ cell tumor evolving to myelodysplasia
Authors: Mascarello James T. , Cajulis Trilla R. , Billman Glenn F. , Spruce Wayne E. 
Published: February 2007

AbstractWe present the case of a 14‐year‐old girl in whom a myelodysplastic syndrome was diagnosed 9 months after surgical resection and chemotherapy for an ovarian germ cell tumor. Cells from her marrow were characterized by trisomy 8 and an isochromosome 12p, a marker that appears to be unique to germ cell tumors. The presence of the same two anomalies in her original tumor was demonstrated by fluorescence in situ hybridization study of interphase cells in paraffin‐embedded tissues and thus provided strong evidence that the two neoplasms had a common clonal origin. © 1993 Wiley‐Liss, Inc.
Clonal karyotypic evolution in an embryonal rhabdomyosarcoma with trisomy 8 as the primary chromosomal abnormality
Authors: Dietrich Claudia U. , Jacobsen Bendt Brock , Starklint Henrik , Heim Sverre 
Published: February 2007

AbstractAn embryonal rhabdomyosarcoma was analyzed cytogenetically. In primary cultures fed a serum‐containing medium, 11 clones with karyotypic abnormalities were found. One had trisomy 8 only. The other 10 clones had trisomy 8 as well as additional evolutionary changes that included trisomy for part or all of chromosome 2, isochromosomes for the short and long arms of chromosome 11, isochromosomes for the long arm of chromosome 8, and extra copies of chromosome 8, some of which had an interstitial deletion in 8q. In those primary cultures that had grown in a chemically defined, serum‐free medium and in all passaged cultures, trisomy 8 was the only aberration. Our findings and a survey of published information point to gain of one chromosome 8 as a frequent primary karyotypic abnormality in embryonal rhabdomyosarcomas. Trisomy for part or all of chromosomes 2 and 11 and additional gains of chromosome 8 material seem to be common secondary changes. © 1993 Wiley‐Liss, Inc.
Ring chromosome 12 resulting from nonrandom telomeric associations with the short arm of chromosome 15 in a cerebellar astrocytoma
Authors: Sawyer Jeffrey R. , Sammartino Gael , Husain M. , Lewis Jane M. , Anderson Bruce , Boop Frederick A. 
Published: February 2007

AbstractRing chromosome 12 was found in an untreated cerebellar astrocytoma apparently resulting from nonrandom telomeric associations involving the short arm of chromosome 15, and both the long and short arms of chromosome 12. The clonal nonrandom telomeric associations of 15p to both ends of the chromosome 12 were transitory, but appear to be the precursor lesion in the evolution to ring chromosome 12 in this tumor. A multistep process in the formation of a ring chromosome resulting from nonrandom telomeric associations to both telomeres is illustrated. © 1993 Wiley‐Liss, Inc.
Extensive genetic alterations in prostate cancer revealed by dual PCR and FISH analysis
Authors: Macoska Jill A. , Micale Mark A. , Sakr Wael A. , Benson Philip D. , Wolman Sandra R. 
Published: February 2007

AbstractThe genetic alterations that underlie prostate tumorigenesis are assumed to comprise gain or loss of specific chromosomal regions, whole chromosomes, or sequence‐specific mutations. Existing data have not demonstrated clear specificity of whole chromosome or regional chromosomal gain or loss that characterizes entire individual malignant lesions, or all malignant lesions, within a cancerous prostate. We have analyzed tissues from 13 patients for target sequences by using PCR and FISH techniques on paired malignant or prostatic intraepithelial neoplastic (PIN) and benign samples (usually from different areas of the same paraffin section). We exercised stringent histologic control over these samples by examining small ( < 5 mm2), discrete regions of sectioned benign, malignant, and PIN tissue. The same histologic region was examined on serial sections by FISH and PCR analysis. The tissues were examined for numerical aberrations involving chromosomes 4 (as a control), 7, 8, 10, and the Y by FISH analysis, and for gain or loss of chromosome 7 and chromosomal arms 8p, 10q, and Yp by PCR analysis. The concurrent application of PCR and FISH to microdissected prostatic tissues yielded evidence of higher frequencies of genetic aberration in prostate cancers than those found with either method alone or by other approaches. These results indicate the power of simultaneous genetic assays that are closely linked to specific tumor histology. © 1993 Wiley‐Liss, Inc.
Carcinogen‐induced amplification of SV40 DNA inserted at 9q12‐21.1 associated with chromosome breakage, deletions, and translocations in human uroepithelial cell transformation in vitro
Authors: Kao Chinghai , Wu Shi‐Qi , Devries Sandy , Reznikoff William S. , Waldman Frederic M. , Reznikoff Catherine A. 
Published: February 2007

AbstractThe fate of integrated SV40 viral genome in SV40‐immortalized human uroepithelial cells (SV‐HUC) during multistep chemical transformation in vitro was studied. We previously reported that exposure of SV‐HUC at passage (P) 15 to the chemical carcinogens 3‐methylcholanthrene (MCA), 4‐aminobiphenyl (ABP), or the N‐hydroxy metabolites of ABP causes tumorigenic transformation and/or neoplastic progression. We report now that these same chemical carcinogens induce amplification of SV40 DNA in SV‐HUC. We used fluorescence in situ hybridization (FISH) to show that this amplification occurs at the SV40 integration site, which was mapped near a common fragile site at 9q12‐21.1 on the der(9)t(8;9) chromosome that is present in all SV‐HUC at the earliest passage studied. Karyotypic analysis, along with FISH, also revealed that all carcinogen‐induced tumors (T‐SV‐HUCs) had breaks at 9q12‐21.1, deletions of 9q12‐21.1→pter, and new derivative chromosomes containing SV40 in the segment 9q12‐21.1→9q34::8q22→8qter. Southern blot analysis, along with FISH, confirmed SV40 genome rearrangements in T‐SV‐HUCs. In contrast, no 9q12‐21.1 breaks were observed in control SV‐HUC. Thus, these results associate 9q 12‐21.1→pter alterations with HUC tumorigenic transformation. In addition, these results indicate for the first time that (carcinogen‐induced) amplification of chromosome‐integrated viral genes may create sites that are prone to breakage, deletions, and translocations. These results suggest a new mechanism by which chemical carcinogens in synergy with a DNA tumor virus could initiate a cascade of events that contribute to the genomic instability associated with tumorigenesis. © 1993 Wiley‐Liss, Inc.
Chromosome abnormalities in non‐small cell lung cancer pleural effusions: Cytogenetic indicators of disease subgroups
Authors: Lukeis Robyn , Ball David , Irving Louis , Garson O. Margaret , Hasthorpe Suzanne 
Published: February 2007

AbstractA cytogenetic study of pleural effusions (PE) containing metastatic or invasive tumor cells from 11 patients with non‐small cell lung cancer (NSCLC) (3 squamous cell carcinomas [SQC] and 8 adenocarcinomas [ADC] including 1 giant cell variant) was performed to identify non‐random chromosome abnormalities. Numerical abnormalities seen in ≥ 30% of cases included gain of chromosomes 7 and 20, and loss of chromosomes 4, 9, 10, 13, 15, 16, 18, 19, 21, and 22. The most frequent structural abnormality involved rearrangement in 1p with breakpoints clustering at 1p10‐p13. Other recurrent breakpoint regions, seen in ≥ 30% of cases, occurred in chromosome regions 3p10‐p21, 3q11‐q25, 6p11‐p25, 6q13‐q23, 7q11‐q36, 9q32‐q34, 11p11‐p13, 11q13‐q24, 13p/14p and/or 15p, 17p and 19p, with, in particular, apparent loss of 6q21‐q27, 3p21‐p26, 7q21‐q22, 9p22‐p24 (shortest regions of common overlap) and 17p. There was also recurrent gain of 1q23‐q44, 8q13‐q24, and 11q13‐q23. These abnormalities were not restricted to a particular histological subtype, with the exception of + 8 and a breakpoint in 9q32‐q34, which were seen only in ADC. The 9q32‐q34 breakpoint observed in 4 ADC PE (including 1 giant cell variant) represents a new observation in NSCLC. These findings, when compared to those reported for primary NSCLC indicate cytogenetic differences between the two which may be associated with pleural invasion of NSCLC. © 1993 Wiley‐Liss, Inc.