bluuebunny/crossref_metadata_2025 huggingface dataset:
Comprehensive screening of the human KRAS2 gene for sequence variants
Authors: Abrams Ezra S. , Murdaugh Susan E. , Lerman Leonard S.
Published: February 2007

To search for mutations in the human KRAS2 oncogene, we have analyzed polymerase chain reaction (PCR) fragments by denaturing gradient gel electrophoresis. We used six different PCR fragments to screen the five coding exons of this gene as well as the splice sites. GC clamps were added to each fragment by means of heteroduplex extension. We infer, from a theoretical analysis in which we employed the computer programs MELT and SQHTX, that virtually any mutation affecting one or a few base pairs in the coding exons or splice sites will be detectable. Thus the system that we describe should allow comprehensive detection of mutations throughout the coding exons and splice sites of the KRAS2 gene. As an example, we show that missense mutations at codons 12, 13, and 61 can be detected; mutant KRAS2 genes isolated from human tumors have been found to contain mutations only at these codons. We also report the discovery of three new polymorphic loci in the KRAS2 gene. We show that PCR reactions containing two or three fragments can be screened in a single lane of a denaturing gradient gel; this dramatically increases the number of base pairs that can be screened per gel. © 1993 Wiley‐Liss, Inc.
Murine radiation myeloid leukaemogenesis: Relationship between interstitial telomere‐like sequences and chromosome 2 fragile sites
Authors: Bouffler Simon , Silver Andy , Papworth David , Coates Julia , Cox Roger
Published: February 2007

While the specific nature of chromosomal fragile sites and their relationship to human leukaemogenesis remain obscure, there is evidence that chromosomal fragility may, in some circumstances, be associated with telomere‐like repeat sequences and that chromosome 2 fragility in the mouse is involved in the initiation of myeloid leukaemia by ionising radiation. Here we describe the molecular cloning and characterisation of two murine telomere‐like sequences, one having an inverted repeat structure and the other a simple tandem repeat organisation. The inverted telomere repeat clone generates an in situ chromosome 2 hybridisation pattern very similar to the distribution of the radiation‐sensitive fragile sites previously found to be associated with leukaemogenic initiation. Furthermore, statistical comparison of the distributions of radiation induced breakpoints and sites of inverted telomere repeat hybridization indicates concordance at all chromosome 2 sites excluding the terminal regions. These data are discussed with respect to mechanisms of radiation‐induced, site‐specific chromosome 2 rearrangement and their implications for leukaemogenic initiation. © 1993 Wiley‐Liss, Inc.
Chromosome painting in acute monocytic leukemia
Authors: Cherif Dorra , Romana Serge , Der‐Sarkissian Hera , Jones Carol , Berger Roland
Published: February 2007

An Alu polymerase chain reaction (PCR) probe specific for chromosome II prepared from the somatic cell hybrid JI was used to analyze karyotypes of eight patients with acute monocytic leukemia (AML‐M5). Chromosome painting confirmed the t(9;II) in one patient and a der(I)t(I;6)t(6;II) in another and allowed the identification of a complex rearrangement involving chromosomes 9, 11, and 17, previously classified as del(II)(q23), in a third patient. An analysis of five patients with AML‐M5 and a normal karyotype did not detect abnormalities of chromosome II. The usefulness of chromosome painting combined with in situ hybridization with probes previously located on particular chromosomes is emphasized. © 1993 Wiley‐Liss, Inc.
Rearrangements of the RARA and PML genes in a cytogenetic variant of acute promyelocytic leukemia
Authors: Baranger L. , Gardembas M. , Hillion J. , Foussard C. , Ifrah N. , Boasson M. , Berger R.
Published: February 2007

Acute promyelocytic leukemia (APL) is usually associated with the translocation t(15;17)(q22;q12‐21), which disrupts the retinoic acid receptor alpha (RARA) gene on chromosome 17 and the PML gene on chromosome 15. We report a patient with typical APL without the common t(15;17). Cytogenetic studies demonstrated a normal appearance of chromosomes 15, while a small marker seemed to be an i(17q—). Molecular analysis showed RARA and PML rearrangements, suggesting that the chromosome abnormality corresponded to a variant translocation. © 1993 Wiley‐Liss, Inc.
Regulation of transcription by the retinoblastoma protein
Authors: Horowitz Jonathan M.
Published: February 2007

The product of the retinoblastoma gene (RB1) is believed to function as a negative regulator of cell growth. Recent experimental results suggest that RB1 may exert its growth‐suppressing activity by regulating the transcription of a variety of growth‐related genes, including FOS, MYC, and TGFB1. A series of biochemical and molecular analyses suggest that RB1 indirectly affects gene expression via cell‐cycle‐regulated interactions with transcription factors, such as E2F and SP1. Determination of the mechanisms regulating such protein‐protein interactions and the identification of additional targets of RB1 function will provide vital insights into the role of this tumor‐suppressor gene in mammalian cell proliferation. © 1993 Wiley‐Liss, Inc.
Breakpoint clusters of the PML gene in acute promyelocytic leukemia: Primary structure of the reciprocal products of the PML‐RARA gene in a patient with t(15;17)
Authors: Dong Shuo , Geng Jie‐Ping , Tong Jia‐Hua , Wu Yu , Cai Jin‐Ren , Sun Guan‐Lin , Chen Shu‐Rong , Wang Zhen‐Yi , Larsen Christian‐Jacques , Berger Roland , Chen Sai‐Juan , Chen Zhu
Published: February 2007

DNA studies of the translocation t(15;17) in acute promyelocytic leukemia (APL) have shown that the retinoic acid receptor alpha (RARA) gene on chromosome 17 is juxtaposed to the promyelocytic leukemia (PML) gene on chromosome 15. The PML breakpoints have been mapped to 3 clusters: bcr1, bcr2, and bcr3. We have examined the PML breakpoint distribution in a series of 33 Chinese patients with APL Twenty‐two patients fell within bcr1, 2 within bcr2, and 9 within bcr3. The primary structure of the reciprocal chromosome translocation joints of one patient and that of their normal counterparts have been determined and compared to those of 2 previously reported cases. These studies revealed possible topoisomerase II cleavage sites close to the breakpoints and suggested implications of DNA attachment sites to nuclear matrix. We propose that these features are relevant to the process of illegitimate recombination generating the translocation. © 1993 Wiley‐Liss, Inc.
Trisomy 7 in nonneoplastic cells
Authors: Johansson Bertil , Heim Sverre , Mandahl Nils , Mertens Fredrik , Mitelman Felix
Published: February 2007

The 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

DNA 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

The 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

Because 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

The 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

Translocations 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

Frequent 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

Wilms' 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

FLT4 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

Cytogenetic 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

We 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

An 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

Ring 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

The 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

The 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

A 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.
Trisomy 7: A potential cytogenetic marker of human prostate cancer progression
Authors: Bandyk Mark G. , Pisters Louis L. , Von Eshenbach Andrew C. , Chung Leland W. K. , Zhao Lian , Liang Jan C. , Troncoso Patricia , Palmer Judy L.
Published: February 2007

We used the fluorescence in situ hybridization (FISH) method to show that chromosome 7 trisomy is associated with the progression of human prostate cancer. Thirty‐six specimens including 15 primary prostate carcinomas, 16 metastatic lesions, and 5 normal prostate tissues, as well as 2 prostate carcinoma cell lines of different tumorigenic potential, were examined for chromosome 7 aneuplaidy. Our results showed that the androgen‐unresponsive tumorigenic cell line PC‐3 exhibited a significantly higher ratio of chromosome 7 to total chromosome number than the androgen‐responsive nontumorigenic cell line LNCaP (P = 0.001). In prostate specimens, the frequency of trisomy 7 cells was significantly increased (P < 0.05) in the advanced stage tumors (C and D1) but not in the early (6) stage tumors or normal prostatic tissue. Furthermore, metastases showed a higher frequency of trisomy 7 cells than primary tumors (P = 0.005). In 2 patients with paired primary and metastatic tumors, trisomy 7 cells increased from 4‐7% in the primary tumors to 42‐45% in the metastatic tumor cells in the bone marrow. Therefore, our data suggest that trisomy 7 may be a common feature associated with local and metastatic progression and serve as a novel marker for human prostate cancer progression. Genes Chrom Concer 9:/9‐27 (1994). © 1994 Wiley‐Liss, Inc.
Molecular and cytogenetic analysis of chromosome 9 deletions in 75 malignant gliomas
Authors: Josefa Bello M. , Pestaña Angel , Rey Juan A. , De Campos Jose M. , Vaquero Jesus , Elena Kusak M. , Sarasa Jose L.
Published: February 2007

A deletion mapping analysis of chromosome 9 has been performed on a series of 75 samples derived from malignant gliomas. A total of 27 tumors displayed different deletions for the loci studied (D9S1, NRASL1, D9S18, IFNA, and IFNB1). In most instances, losses involving the markers located on the short arm of chromosome 9 were observed, and only two samples were characterized by losses of the short and long arms. Either partial or complete homozygous deletions of IFN genes were observed in 15 cases, and 12 other samples showed hemizygous deletions for these genes. The results show that the 9p abnormalities are not exclusive to high‐grade astrocytic tumors, as some low‐grade samples (two astrocytomas grade II and six oligodendrogliomas) displayed this anomaly which, in a few instances, was the sole abnormality detected. Genes Chrom Cancer 9:33‐41 (1994). © 1994 Wiley‐Liss, Inc.
Chromosome abnormalities in pancreatic adenocarcinoma
Authors: Griffin Constance A. , Long Patricia P. , Morsberger Laura A. , Douna‐Issa Fadia , Hruban Ralph H. , Yeo Charles J.
Published: February 2007

Adenocarcinoma of the pancreas is the fifth most common cause of cancer deaths in the United States, yet few cytogenetic studies of this tumor have been reported. We analyzed 26 primary tumors to identify which chromosome abnormalities occur most frequently in this neoplasm. One carcinoma was well differentiated and mucin producing, 18 were moderately well differentiated, and seven were poorly differentiated. Only normal karyotypes were obtained from nine carcinomas. The remaining 17 carcinomas frequently had normal metaphase cells in addition to simple to highly complex karyotypes. The modal chromosome number in 20 carcinomas was diploid or near‐diploid; four carcinomas had both a major near‐diploid and near‐triploid or near‐tetraploid component, and two were near‐tetraploid. Numerical abnormalities included loss of whole copies of chromosomes 6, 17, and 18, and gains of chromosome 20. Structural abnormalities were frequent, with 1p, 2p, 3p, 4q, 6q, 7q, 1 1q, and 17p recurrently involved. Results of this study were combined with karyotypes of 19 other primary adenocarcinomas of the pancreas reported in the literature. The combined data involving 1 17 breakpoints suggest that careful analysis of chromosome 20, proximal 1 q. 6q, proximal 8p. and proximal 17p could be productive in defining genes involved in adenocarcinoma of the pancreas. Genes Chrom Cancer 9:93‐100 (1994).© 1994 Wiley‐Liss, Inc.
At least two different regions are involved in allelic imbalance on chromosome arm 16q in breast cancer
Authors: Cleton‐Jansen Anne‐Marie , Moerland Elna W. , Kuipers‐Dijkshoorn Net J. , Cornelisse Cees J. , Devilee Peter , Callen David F. , Sutherland Grant R , Hansen Bettine
Published: February 2007

Loss of heterozygosity (LOH) or allelic imbalance, the latter term referring to both loss and gain of an allele, on the long arm of chromosome 16 has been repeatedly found in cancers of, e.g., the breast and prostate. This indicates the presence of one or more tumor suppressor genes on 16q. To locate the gene(s) more precisely, a detailed allelic imbalance map of 20 polymorphic markers on this chromosome arm was made for 79 sporadic breast carcinomas. LOH of one or more markers was found in 63% of the tumors. Some had allelic imbalance on a region of 16q which failed to overlap with the LOH in other tumors. We therefore assigned two separate “smallest regions of overlap” to 16q and suggest that this chromosome arm contains at least two different tumor suppressor genes. Genes Chrom Cancer 9:101‐107 (1994).© 1994 Wiley‐Liss, Inc.
Constitutional DNA‐level aberrations in chromosome 22 in a patient with multiple meningiomas
Authors: Deprez Ronald H. Lekanne , Groen Nicole A. , Louz Derrick , Van Der Kwast Theo H. , Zwarthoff Ellen C. , Hagemeijer Anne , Van Drunen Ellen , Bootsma Dirk , Koper Jan W. , Avezaat Cees J. J.
Published: February 2007

We describe a patient who developed multiple meningiomas but had no clear evidence of neurofibromatosis type 2. Four of the tumors, derived from three different sites, were analyzed cytogenetically and/or at the DNA level using chromosome 22 specific probes. All four tumors showed loss of the same copy of chromosome 22. On the chromosome that was retained in the tumors, we found two constitutional aberrations, a 1.5 kb deletion and a point mutation. The patient had inherited both alterations from her father. The father has not developed any meningiomas so far but he has been treated for a well‐differentiated adenocarcinoma of the lung and a brain metastasis from this tumor. The mother and 75 unrelated individuals did not show any of the chromosome 22 alterations. The multiple tumors found in the patient suggest that she has a predisposing gene for the development of meningiomas. The finding that all investigated tumors lost the same, constitutionally normal copy of chromosome 22 could indicate that the predisposing gene resides on chromosome 22 and was affected by the constitutional mutations. Genes Chrom Cancer 9:124‐128 (1994).© 1994 Wiley‐Liss, Inc.
Amplification of the anonymous marker D17S67 in malignant astrocytomas
Authors: Bijlsma Emilia K. , Westerveld Andries , Hulsebos Theo J. M. , Leenstra Sieger , Bosch D. Andries
Published: February 2007

Loss of heterozygosity (LOH) for chromosome arms 9p, 10p, 10q, and 17p and amplification of the epidermal growth factor receptor (EGFR) gene have been identified as frequent genetic changes in malignant astrocytomas. We have found amplification of the anonymous marker D17S67 on chromosome arm 17p in 10% (3 of 30 cases) of astrocytomas of the highest malignancy grade. The tumors with D17S67 amplification displayed other genetic changes on chromosome 17, including additional amplifications and deletions. All three patients with D17S67 amplification developed severe brain edema and died within I month after operation. Genes Chrom Cancer 9:148‐152 (1994). © 1994 Wiley‐Liss, Inc.
A 3‐Mb physical map of the chromosome region 8p21.3‐p22, including a 600‐kb region commonly deleted in human hepatocellular carcinoma, colorectal cancer, and non‐small cell lung cancer
Authors: Fujiwara Yoshiyuki , Ohata Hiroyuki , Emi Mitsuru , Okui Keiko , Koyama Kumiko , Tsuchiya Eiju , Nakajima Toshifusa , Monden Morito , Mori Takesada , Kurimasa Akihito , Oshimura Mitsuo , Nakamura Yusuke
Published: February 2007

To isolate a putative tumor suppressor gene(s), we have constructed a physical map and a detailed deletion map of chromosome region 8p21.3‐p22, where loss of heterozygosity (LOH) has been frequently seen in human hepatocellular carcinomas (HCC), colorectal cancers (CRC), and non‐small cell lung cancers (NSCLC). The smallest commonly deleted region at 8p21.3‐p22 in HCC and CRC was between the loci defined by CI8‐245 and CI8‐2644; in NSCLC, a region between CI8‐1051 and CI8‐2644 was commonly deleted. A contiguous physical map of 12 cosmid markers in the 8p21.3‐p22 region was constructed by means of multi‐color fluorescence in situ hybridization (FISH) and pulsed‐field gel electrophoresis (PFGE). On the basis of this physical map, which spans roughly 3.1 Mb, the estimated sizes of the commonly deleted regions were at most 1.2 Mb in HCC and CRC and 0.6 Mb in NSCLC. As four of the 12 physically ordered markers are located within the 0.6 Mb region commonly deleted in all three tumor types, nearly one fourth to one fifth of the target region has already been covered with cosmid inserts. Genes Chrom Cancer 10:7–14 (1994). © 1994 Wiley‐Liss, Inc.
Identification of genetically aberrant cell lineages in Wilms' tumors
Authors: Weremowicz Stanislawa , Kozakewich Harry P. , Haber Daniel , Park Seon , Morton Cynthia C. , Fletcher Jonathan A.
Published: February 2007

Most Wilms' tumors contain several predominant cell types, of which a primitive blastemal population is often the most prominent. Other typical components include undifferentiated mesenchymal and epithelial cells, but it has not been demonstrated that these components are neoplastic. We used a combined cytogenetic and fluorescence in situ hybridization approach to determine the clonal relationship of different cell populations within six Wilms' tumors. Clonal numerical chromosome aberrations in three Wilms' tumors were found in blastemal cells, but not in mesenchymal cells. Loss of one WTl allele in two other tumors was detected in both blastemal and mesenchymal cells. Tetrasomy 18 in a sixth case was observed in mesenchymal and epithelial cells; blastemal cells could not be evaluated in this tumor. These findings demonstrate that mesenchymal and epithelial cells in some Wilms' tumors are neoplastic. Different histologic components in some Wilms' tumors derive from a single chromosomally aberrant ancestor which is most likely to be the primitive blastemal cell. Genes Chrom Cancer 10:40–48 (1994). © 1994 Wiley‐Liss, Inc.
Induction of senescence and control of tumorigenicity in BK virus transformed mouse cells by human chromosome 6
Authors: Gualandi Francesca , Morelli Cristina , Pavan Jorge V. , Rimessi Paola , Sensi Alberto , Bonfatti Alessandra , Gruppioni Rita , Possati Laura , Stanbridge Eric J. , Barbanti‐Brodano Giuseppe
Published: February 2007

Viral transformation models may be useful to detect and map human tumor suppressor genes. BK virus (BKV), a human papovavirus, readily transforms rodent cells but is unable to transform human cells, suggesting that oncosuppressive functions expressed in human cells control BKV oncogenic activity. We have transferred human chromosome 6 to BKV‐transformed mouse pRPcTlssI cells. The great majority of the colonies growing in selective medium degenerated by senescence. Only five hybrid pRPcTIssI/H6 clones maintained the immortalized phenotype of the recipient cell line. All the immortalized clones had two common regions of deletion involving bands 6q21–22 and the SOD2 gene in 6q25. Senescent colonies carried an intact chromosome 6. A specific human sequence in 6q21–22 was amplified by PCR in senescent cells, suggesting that this region harbors a gene inducing senescence. The SOD2 deletion confirms recent data on the role of the Mn‐dependent superoxide dismutase in inhibition of proliferation. The monochromosomic hybrids bearing a deleted chromosome 6 showed a reverted phenotype in vitro and a significantly longer latency period before they were tumorigenic in nude mice, indicating the presence of a tumor suppressor gene in the residual regions of chromosome 6. Molecular mapping suggests that this gene is located in 6q27. The BKV transformation model detects genes inducing senescence and tumor suppressor genes on human chromosome 6 and may represent a useful system to isolate and clone such genes. Genes Chromosom Cancer 10:77–84 (1994). © 1994 Wiley‐Liss, Inc.
Cell lineage involvement of recurrent chromosomal abnormalities in hematologic neoplasms
Authors: Knuutila Sakari , Teerenhovi Lasse , Larramendy Marcelo L. , Elonen Erkki , Franssila Kaarle O. , Nylund Stella J. , Timonen Time , Heinonen Kristiina , Mahlamäki Eija , Winqvist Robert , Ruutu Tapani
Published: February 2007

Analysis of most hematologic neoplasms indicates the involvement of one or more cell lineages in the bone marrow and/or the blood but rules out the involvement of all lineages in any one neoplasm. It is important to detect lineage involvement in order to clarify which stem cells are involved in leukemia, to predict prognosis, and to select appropriate treatment. Our aim was to study the cell lineage involvement of some of the recurrent chromosomal abnormalities seen in hematological neoplasms. The direct morphology‐antibody‐chromosomes (MAC) method was used. The deletion 20q in myeloproliferative diseases (MPD), the deletion of 5q and t(1;7) in myelodysplastic syndromes (MDS), and t(3;3) in acute myeloid leukemia subtype M7 (AML‐M7) were seen in all or at least in two myeloid lineages. These were interpreted as stem cell abnormalities. Deletion 13q in MPD, t(8;21) in AML‐M2 and t(15;17) in AML‐M3 were seen in granulocytic lineages only; t(14;18) in non‐Hodgkin's lymphoma and trisomy 12 as the sole abnormality in chronic lymphocytic leukemia (B‐CLL) were seen only in immunoglobulin light chain clonal B cells; inversion 14 in T‐CLL was seen only in T cells, whereas t(15;14) in acute lymphocytic leukemia with eosinophilia (ALL‐EO) was seen in lymphoid stem cells but not in mature granulocytes or lymphocytes. Additional abnormalities (in addition to the Philadelphia chromosome) in chronic myeloid leukemia (CML) were seen in all myeloid cell lineages and also in mature granulocytes, B cells, and large granular lymphocytes. Abnormalities in Hodgkin's disease were restricted to CD30‐positive Reed‐Sternberg cells. Trisomy 8 and monosomy 7 are abnormalities that may be present in either stem cells or any of the single cell lineages. Genes Chromosom Cancer 10:95–102 (1994). © 1994 Wiley‐Liss, Inc.
Some desmoid tumors are characterized by trisomy 8
Authors: Cin Paola Dal , Sciot Raf , Aly Magdy S. , Delabie Jan , Stas Margareta , De Wever Ivo , Van Damme Boudewijn , Van Den Berghe Herman
Published: February 2007

Ten desmoid tumors were examined by chromosome banding analysis and by in situ hybridization on short‐term cultures and frozen sections. Trisomy 8 was detected in four out of ten tumors, of which only one had shown trisomy 8 by karyotype analysis. Since trisomy 8 has been reported in superficial fibromatoses, which are clinically distinct but histologically similar to desmoid tumors, the occurrence of trisomy 8 in both may be a further indication of a close relationship. Genes Chromosom Cancer 10:131–135 (1994). © 1994 Wiley‐Liss, Inc.
TP53 alterations and clinical outcome in low grade astrocytomas
Authors: Kraus Jürgen A. , Bolln Carsten , Wolf Helmut K. , Neumann Jürgen , Kindermann Dietmar , Fimmers Rolf , Forster Frank , Baumann Axel , Schlegel Uwe
Published: February 2007

Thirty‐eight WHO grade II astrocytomas and 10 malignant recurrent gliomas in these patients were examined for the presence of TP53 alterations. Seventeen/38 low grade astrocytomas and 6/10 malignant recurrent tumors harbored mutations of the gene detected by SSCP analysis and direct sequencing of PCR products. TP53 mutations in five out of six high grade mutant tumors were already present in the corresponding low grade astrocytomas. In two cases, TP53 mutations present in the low grade astrocytoma could not be demonstrated in the recurrent glioma. Immunohistochemistry with two different antibodies to the human TP53 protein revealed nuclear immunoreaction of tumor cells in 11/38 low grade and in 8/10 recurrent tumors. There was no correlation between the presence of TP53 alteration and clinical course. We conclude that, although TP53 mutations are detectable in a substantial fraction of WHO grade II astrocytomas, they do not appear to play a role in the malignant progression of these tumors and they are not of prognostic significance. Genes Chromosom Cancer 10:143–149 (1994). © 1994 Wiley‐Liss, Inc.
Characterization of homogeneously staining regions in a small cell lung cancer cell line, using in situ hybridization with an MYCN probe
Authors: Dietzsch Erin , Lukeis Robyn E. , Vrazas Vickie , Hasthorpe Suzanne , Garson O. Margaret
Published: February 2007

The cell line CIPL38 was derived from the pleural effusion of a patient with small cell lung cancer. The karyotype was hyperdiploid and complex with a variable number of marker chromosomes. Two of the markers had large homogeneously staining regions (hsr), which were shown to consist of amplified MYCN by in situ hybridization. One hsr bearing a marker chromosome could not be identified with G‐banding, but the other was situated on a der(14). This was elucidated further with FISH analysis, which enabled the identification of sequences of chromosome I involved in a complex rearrangement with chromosome 14 and the hsr. Genes Chromosom Cancer 10:213–216 (1994). © 1994 Wiley‐Liss, Inc.