bluuebunny/crossref_metadata_2025 huggingface dataset:
Two malignant peripheral primitive neuroepithelial tumor cell lines established from consecutive samples of one patient: Characterization and cytogenetic analysis
Authors: Kees Ursula R. , Ford Jette , Willoughby Michael L. N. , Rudduck Christina , Margaret Garson O. , Spagnolo Dominic , Papadimitriou John
Published: February 2007

A 6‐year‐old girl presented with a tumor of the right shoulder involving bone, adjacent soft tissue, and regional lymph nodes. The conventional histologic diagnosis was ambiguous, initially suggesting lymphoma. After relapse on lymphoma therapy, reevaluation with additional multiple diagnostic techniques performed on the biopsy tissue and on two cell lines derived from the biopsies established the diagnosis of a primitive neuroepithelial tumor of bone and soft tissue. This was strongly supported by 1) focal rosette formation by the tumor cells and positive immunostaining for neuron‐specific enolase and synaptophysin, with absent staining for leukocyte common antigen; 2) at the ultrastructural level, formation of cellular processes containing microtubules, a paucity of neurosecretory granules, absence of synaptic junctions, formation of long “intermediate” junctions between cells, and, in culture, widespread development of rosettes; 3) marked surface positivity to W 6/32 and negativity to HSAN 1.2 antibodies; and 4) elevated expression of MYC and lack of overexpression of MYCN oncogenes. Numerical and structural abnormalities were present in the karyotype, but the expected t(11;22)(q24;q12) was not present in the tumorinvolved marrow or in either of the established tumor cell lines, although there was an interstitial deletion of 11q involving breakpoints in q21 and q23.
Ordering of six polymorphic dna markers important in the delineation of 3p deletions in neoplasia
Authors: Heppell‐Parton Amanda C. , Rabbitts Pamela H. , Albertson Donna G.
Published: February 2007

Using fluorescence in situ hybridisation (FISH) the chromosomal location and relative order of six human chromosome 3 probes has been determined. The sensitivity of the technique has enabled the relative mapping of probes carrying inserts as small as 500 basepairs (bp), thus allowing the following proximal–distal probe order to be proposed: D3S30 (3p13–14), D3S4 (3p13–14), D3S2 (distal 3p14), D3S32 (3p21), D3S48E (3p21–23), and D3S11 (3p22–23). These data combined with the deletion mapping data of other researchers raise the possibility that the loss of more than one region of the short arm of chromosome 3 may be important in the development of small cell lung cancer.
Retinoblastoma gene deletions in b‐cell chronic lymphocytic leukemia
Authors: Liu Yie , Grandér Dan , Einhorn Stefan , Söderhäll Stefan , Juliusson Gunnar , Gahrton Gösta
Published: February 2007

Approximately 10% of B‐cell chronic lymphocytic leukemia (B‐CLL) cases have structural chromosomal aberrations involving band 13q14. To evaluate a possible role of RB1 gene deletions in B‐CLL we investigated the malignant cells of 27 patients by molecular genetic and cytogenetic techniques. Four of the cases had chromosomal aberrations that involved 13q14 (including one case with a 13q14 deletion that was observed in a single metaphase cell), and 11 had other chromosomal abnormalities, whereas the malignant cells of 12 patients were either cytogenetically normal or failed to divide in vitro. Eight patients (30%) were found to have hemizygous deletions of the RB1 gene. These cases included all four patients with chromosomal changes at 13q14, but also three patients without chromosome abnormalities and one case with a chromosomal aberration not involving 13q. The deletions were interstitial in all cases but one, as defined by probes located centromeric and telomeric of the RB1 locus. Inactivation of RB1 may thus be a significant event in the development of some B‐CLL clones.
Trisomy 8 in philadelphia chromosome (ph1)‐negative cells in the course of ph1‐positive chronic myelocytic leukemia
Authors: Casali Monica , Truglio Fabrizio , Maserati Emanuela , Pasquali Francesco , Milone Giuseppe , Raimondo Francesco Di , Parrinello Gisella
Published: February 2007

A female patient with chronic myelocytic leukemia (CML) in chronic phase after busulfan and interferon treatment had four different cell lines in her bone marrow. In addition to cells with a normal karyotype there were cells with the Philadelphia chromosome (Ph1), cells with trisomy 8 and a Ph1, and cells with trisomy 8 as the sole anomaly.
Molecular confirmation of BCR‐ABL fusion in a chronic myeloid leukemia with a complex translocation involving chromosomes 9, 15, and 22
Authors: Tharapel Sugandhi A. , Vnencak‐Jones Cindy L. , Whitlock James A. , Jain Rajiv
Published: February 2007

We performed molecular studies to resolve the status of BCR and ABL in the bone marrow cells of a CML patient with a Ph chromosome resulting from a complex translocation involving chromosomes 9, 15, and 22. DNA digestion with BamHL, Hindlll, and Bglll, followed by hybridization to a bcr‐specific 32P‐labeled probe, showed a rearranged banding pattern confirming the involvement of the bcr, locus in the translocation. Furthermore, total cellular RNA isolated from the marrow was subjected to reverse transcription into cDNA and amplified by PCR with primers specific for BCR‐ABL fusion cDNA. The amplified products obtained from this patient and from a CML patient with the standard t(9;22) were both of the expected length of approximately 317 bp.
Improved technique for short‐term culture and cytogenetic analysis of human breast cancer
Authors: Pandis Nikos , Heim Sverre , Bardi Georgia , Limon Janusz , Mandahl Nils , Mitelman Felix
Published: February 2007

Various growth media and procedures for tissue disaggregation and culturing were tested with regard to cell attachment, the type of cells to grow out, and the emergence of cytogenetically abnormal clones in cultures of 20 primary breast carcinomas. Clonal chromosome abnormalities were detected in 16 cases (80%). Our findings allow us to suggest a series of modifications of existing culturing and chromosome preparation techniques for breast cancer cytogenetic analysis. The improvements include: (1) combined mechanical and enzymatic disaggregation of the tumor samples, (2) initiation of short‐term cultures in plastic flasks that have a Primaria‐modified tissue culture surface or have been coated with Vitrogen 100, (3) use of serum‐free growth medium, CDM‐5, but with temporary (24 hours) enrichment with 20% FBS if rapid cell attachment is not achieved, (4) partial and sequential harvesting of the cultures, and (5) use of minimal volumes of hypotonic and fixative solutions during harvesting.
Molecular characterization of a large homozygous deletion in the small cell lung cancer cell line U2020: A strategy for cloning the putative tumor suppressor gene
Authors: Latif Farida , Tory Kalman , Modi William S. , Graziano Stephen L. , Gamble Gary , Douglas Jenny , Heppell‐Parton Amanda C. , Rabbitts Pamela H. , Zbar Berton , Lerman Michael I.
Published: February 2007

Homozygous deletions are instrumental in the detection and cloning of tumor suppressor genes. We report the isolation and characterization of 39 new single‐copy probes saturating a submicroscopic homozygous deletion detected in the DNA of the small cell lung cancer (SCLC) cell line U2020. The probes were selected from a large collection, covering the entire length of chromosome 3 with an estimated average spacing of 100–150 kb. Based on the number of probes in the deletion and the probe density, the size of the U2020 submicroscopic deletion was estimated to be in the range of 4–7 megabases. Among the deleted loci, 17 showed conservation across species, probably representing potential coding gene sequences. By genetic and physical mapping of a large randomly chosen fraction of the deleted probes, we defined the location of the U2020 deletion within chromosome band 3p 12. Our cloning strategy is based on narrowing the region of interest by eliminating probes that retain heterozygosity in SCLC samples, thus selecting for probes in the region of common loss.
Molecular analysis of 12 patients with the t(8;2l) translocation and M2 acute myelogenous leukemia
Authors: Yaspo Marie‐Laure , Theophile Didier , Aurias Alain , Créte Nathalie , Créau‐Goldberg Nicole , Bastard Christian , Suberville Anne‐Marie , Valensi Françoise , Viguier Franck , Berger Roland , Sinet Pierre‐Marie , Delabar Jean‐Maurice
Published: February 2007

The t(8;21)(q22;q22) is a nonrandom cytogenetic abnormality associated with acute myelogenous leukemia of the M2 subtype (FAB classification). The 8q‐ and 21q+ derivative chromosomes have previously been isolated in somatic cell hybrids and used to map the anonymous sequences D21S65 and D21S17, which were proximal and distal, respectively, to the breakpoint on chromosome 21. DNA from a series of 12 t(8;21) patients and 7 controls was analyzed by pulsed field gel electrophoresis. Physical linkage of probes D21S65 and D21S17 on a 2100 kb Nrul fragment was established by partial digestion experiments. In all the patients, the translocation generated a rearranged D21S65 Nrul fragment of 650 to 750 kb, suggesting heterogeneity in the breakpoints. This heterogeneity was confirmed by using BssHII, Sacll, and Eagl enzymes. Our results are consistent with the presence of a 100 Kb breakpoint cluster region on chromosome 21 encompassing the AMLI gene. Interestingly, in half of the patients, demethylation of an Nrul site located 7 kb proximal to the last exon of the AMLI gene occurred on the nontranslocated chromosome 21.
Molecular characterization of chromosome 22 deletions in schwannomas
Authors: Bijlsma Emilia K. , Brouwer‐Mladin Roma , Bosch D. Andries , Westerveld Andries , Hulsebos Theo J. M.
Published: February 2007

Schwannomas are tumors of the cranial, spinal, and peripheral nerve sheaths that originate from Schwann cells. Acoustic neurinomas are the most frequent cranial schwannomas. They might develop sporadically or in the context of neurofibromatosis type 2 (NF2). Loss of part or all of chromosome 22 is frequently found in acoustic schwannomas, suggesting that the NF2 gene is a tumor suppressor gene involved in the genesis of these tumors. Only a few spinal schwannomas have been molecularly characterized so far, showing that chromosome 22 loss might also occur in these tumors. Here we present the molecular analysis of chromosome 22 in 23 acoustic schwannomas and nine schwannomas of other locations (including other cranial nerves and spinal and peripheral nerves). Most of these tumors were from sporadic cases. Multiple schwannomas of various locations were analyzed in two patients with NF2. We found partial or complete monosomy for chromosome 22 in 22% of the acoustic schwannomas and 55% of the non‐acoustic schwannomas. The tumors with partial monosomy included four with terminal deletions and one with a deletion of the centromeric part of the long arm of chromosome 22. The region between the βB2‐1 crystallin locus (CRYB2A) and the myoglobin locus (MB) was commonly deleted in these tumors. Our studies suggest that a schwannoma‐related tumor suppressor gene within this region, which might be the NF2 gene, is involved in the development of schwannomas of various locations in the nervous system. Our studies indicate that the second hit in the genesis of different schwannomas within one (predisposed) NF2 patient occurs independently and via different mechanisms.
Characterization of the translocation breakpoint sequences of two DEK‐CAN fusion genes present in t(6;9) acute myeloid leukemia and a SET‐CAN fusion gene found in a case of acute undifferentiated leukemia
Authors: Von Lindern Marieke , Breems Dimitri , Van Baal Sjozèf , Adriaansen Henk , Grosveld Gerard
Published: February 2007

The t(6;9) associated with a subtype of acute myeloid leukemia (AML) was shown to generate a fusion between the 3′ part of the CAN gene on chromosome 9 and the 5′ part of the DEK gene on chromosome 6. The same part of the CAN gene appeared to be involved in a case of acute undifferentiated leukemia (AUL) as well, where it was fused to the SET gene. Genomic sequences around the translocation breakpoint were determined in two t(6;9) samples and in the case of the SET‐CAN fusion. Although coexpression of myeloid markers and terminal deoxynucleotidyl transferase was shown to be one of the characteristics of t(6;9) AML, no addition of random nucleotides at the translocation breakpoint could be found. In addition, the breakpoint regions did not reveal heptamer‐nonamer sequences, purine‐pyrimidine tracts, a chi‐octamer motif, or Alu repeats. The sequence in which the translocation breakpoints occurred was enriched in A/T. Notably, the specific introns in which clustering of breakpoints occurs in DEK and CAN both contain a LINE‐1 element. As LINE‐1 elements occur with a moderate frequency in the human genome, the presence of such an element in both breakpoint regions may be more than coincidental and may play a role in the translocation process.
The der(II) chromosome contains the critical breakpoint junction in the 4;11, 9;11, and 11;19 translocations in acute leukemia
Authors: Rowley Janet D.
Published: February 2007

Translocations involving 11q23 are recurring abnormalities in human acute leukemia cells of either lymphoid or myeloid lineage. Analysis of 13 variant translocations associated with four of these [t(4; 11), t(6; 11), t(9; 11) and t(11; 19)] reveals that the der(11) chromosome is conserved in all of them and therefore contains the critical genetic rearrangement. The MLL gene (myeloid/ lymphoid leukemia) is involved in each of these translocations. It is transcribed from centromere to telomere. The present analysis indicates that the 5′ region of MLL on the der(11) is juxtaposed to the coding sequences of genes on each of the other translocation partners.
Rearrangement of the transcription factor gene CHOP in myxoid liposarcomas with t(12;16)(q13;p11)
Authors: Åman Pierre , Ron David , Mandahl Nils , Fioretos Thoas , Heim Sverre , Arheden Kristina , Willén Helena , Rydholm Anders , Mitelman Felix
Published: February 2007

Most myxoid liposarcomas (MLS) are characterized cytogenetically by a t(12; 16)(q13;p11). It is reasonable to assume that this translocation corresponds to the consistent rearrangement of one or two genes in 12q 13 and/or 16p11, and that the loci thus affected are important in the normal control of fat cell differentiation and proliferation. We have used Southern blot technique to test whether a gene of the CCAAT/enhancer binding protein (C/EBP) family, CHOP, which maps to 12q13 and is assumed to be involved in adipocyte differentiation, could be the 12q gene in question. Using a cDNA probe that spans the CHOP coding region, we detected one rearranged and one wild type allele in nine of nine MLS with t(l2;l6). Using PCR generated, site‐specific probes corresponding to the non‐coding exons 1 and 2 and intron 2 of CHOP, rearrangements in five of seven tumors mapped to the 2.4 and 1.6 kbp Pstl fragments that contain the first two exons and introns of the gene and the upstream promoter region. In contrast to the findings in MLS, no tumor without a t(12;16) exhibited aberrant CHOP restriction digest patterns. These tumors included one highly differentiated liposarcoma with abnormal karyotype but no involvement of 12q 13, seven lipomas with various cytogenetic aberrations of 12q 13–15, two uterine leiomyomas with t( 12; 14) (q 14–15;q23–24), and one hemangiopericytoma and one chondroma, both of which also had 12q 13 changes. These findings demonstrate that the 12q breakpoint of the t( 12;16) in MLS differs from those in the other tumors investigated, even in cases with no cytogenetically visible differences in breakpoint position, that CHOP rearrangement is specific for MLS, and that the breakpoints cluster to the 5′ region of the gene. We assume that the CHOP alteration is an important step in MLS tumorigenesis and speculate that this is achieved by interference with the normal function of the C/EBP family of transcription factors.
Tumor‐associated karyotypic lesions coselected with in vitro macrophage differentiation
Authors: Alexander Bruce , Berger Roland , Day Lesley M. , Hogarth P. Mark , Feneziani Anthony , Cook Wendy D.
Published: February 2007

Several cytogenetic lesions in chromosomes 2, 5, 12, and 16 have been repeatedly coselected with in vitro macrophage differentiation in a clonal murine thymic tumor cell line. Parental‐type subclones, which show an extremely immature hemopoietic phenotype, do not carry the aberrations. The frequency of the stable differentiated variants is elevated by 5‐azacytidine and bromodeoxyuridine, consistent with chromosome breakage being responsible for the phenotype. The frequency is also raised by dexamethasone. Since variants are 300–3,000‐fold more resistant to dexamethasone than parental clones, we interpret this to be largely due to selection. Three of the lesions, on chromosome 2, match those previously described as associated specifically with in vivo‐generated murine myeloid tumors, induced by X irradiation and corticosteroid treatment. Several implications follow from these observations. (I) In vitro differentiation in clonal tumor cell lines can be used to select for tumor‐associated lesions. This should allow genetic and molecular analysis of the chromosome 2 lesions and of others that may pinpoint genes critical to macrophage differentiation and transformation. (2) Myeloid and lymphoid tumors that occur in response to X irradiation may diverge from a common initiating tumor. (3) The hemopoietic lineage switch phenomenon, previously described by several authors, may be caused by similar or identical chromosome aberrations.
Correlation of cytogenetic analysis and loss of heterozygosity studies in human diffuse astrocytomas and mixed oligo‐astrocytomas
Authors: Ransom David T. , Ritland Steven R. , Moertel Cheryl A. , Dahl Richard J. , O'Fallon Judith R. , Scheithauer Bernd W. , Kimmel David W. , Kelly Patrick J. , Olopade O. I. , Diaz Manuel O. , Jenkins Robert B.
Published: February 2007

The aims of this study were to correlate cytogenetic studies and molecular genetic loss of heterozygosity (LOH) analyses in human astrocytomas and mixed oligo‐astrocytomas, and to locate putative tumor suppressor genes on chromosome 10. Paired blood and tumor samples from 53 patients were analyzed. The tumors included 45 diffuse astrocytomas (39 grade 4, 4 grade 3, and 2 grade 2), 1 astroblastoma, and 7 mixed oligo‐astrocytomas (2 grade 4,4 grade 3, and 1 grade 2). By cytogenetic analyses the most common numeric chromosome abnormalities were +7, −10, −13, −14, −17, +19, −22, and −Y. The most common structural abnormalities involved chromosome arms 1p, 1q, 5p, and 9p. By LOH and dosage analysis the most common molecular genetic abnormalities were of chromosome arms 5p, 6p, 7q, 9p, 10p, 10q, 13q, 14q, 17p, and 19p. When the results of all methods were combined, the most commonly abnormal chromosomes were, in descending frequency, 10, Y, 17, 7, 13, and 9. In 80 percent of cases the cytogenetic and molecular genetic studies were concordant. LOH studies were more sensitive in detecting loss of genetic material than cytogenetic analyses and accounted for 60% of the discordant results. When there were structural abnormalities, such as translocations or inversions, cytogenetic analysis was more sensitive in detecting an abnormality than molecular genetic studies. In addition to the 24 tumors which appeared to lose an entire copy of chromosome 10, there were 10 tumors with molecular genetic or cytogenetic evidence of loss of only a portion of chromosome 10. The genetic analyses of these tumors suggest that there are 2 regions on chromosome 10 that may contain potential tumor suppressor genes. One lies distal to locus D10S22 from 10q22 to 10qter, and the other lies proximal to locus TSTI on the 10q arm near the centromere or on the 10p arm. © 1992 Wiley‐Liss, Inc.
Complementarity of interphase and metaphase chromosome analysis in human renal tumors
Authors: Wolman Sandra R. , Waldman Frederic M. , Balazs Margit
Published: February 2007

Fluorescence in situ hybridization (FISH) was used as a complement to earlier cytogenetic studies of human renal tumors. Chromosome‐specific para‐centromeric probes were applied to cells disaggregated from tissue blocks of tumors, fresh samples from which had yielded cytogenetic results after short‐term culture. Cells were dissociated from thick sections of paraffin‐embedded, formalin‐fixed tissues. Biotin‐labeled probes specific for chromosomes 1, 3, 7, 11, 12, 15, 17, and the Y chromosome were applied in individual cases and were detected by fluorescence. Probes for chromosomes 1, 7, and 17 yielded clean signals with disomic control frequencies near 90%, and 97% of controls showed a single bright spot for the Y chromosome. The 9 cases selected all provided ample numbers of dissociated cells which were hybridized successfully, although some chromosomal signals were poor in individual cases. Abnormal copy numbers of chromosomes 1 and/or 17, not identified in culture, were observed in 7 cases. Trisomy 7 observed in culture was substantiated by FISH on the original tissues, as was loss of the Y, in each of 4 cases, respectively. Our results include limited validation of culture cytogenetics, evidence of selection in culture of tumor subpopulations, and demonstration that interphase cytogenetics by FISH is applicable to archival tissue blocks after prolonged periods of storage. Conditions of culture before harvest and inherent heterogeneity within tumors permit selection for nonrepresentative subgroups within tumors and emphasize the need for multiple approaches to evaluation. © 1993 Wiley‐Liss, Inc.
Cytogenetic findings in pediatric adipose tumors: Consistent rearrangement of chromosome 8 in lipoblastoma
Authors: Fletcher Jonathan A. , Kozakewich Harry P. , Schoenberg Marlena L. , Morton Cynthia C.
Published: February 2007

Characteristic cytogenetic aberrations have been reported in adult lipomas and liposarcomas, but few karyotypes have been reported for pediatric adipose neoplasms. In this report we describe a consistent rearrangement, der(8)(pter→q13::q24.1→qter), in 2 of 3 lipoblastomas. A similar der(8) was present in the only other published lipoblastoma karyotype, but this der(8) has not been reported in lipomas, liposarcomas, or nonadipose solid tumors. We investigated the potential specificity of der(8)(pter→q13::q24.1→qter) by karyotyping an unselected series of nonlipoblastoma adipose tumors in children and young adults. The series included 14 lipomas, 2 atypical lipomas (“well‐differentiated liposarcomas”), and 2 angiomyolipomas; der(8) was not found in any tumor from this series. Three lipomas, however, contained rearrangements in the region of chromosome band 12q14, as has been described frequently in adult lipomas. Because clinical features in lipoblastoma can mimic those in liposarcoma, recognition of der(8)(pter→q13::q24.1→qter) is of potential diagnostic relevance. © 1993 Wiley‐Liss, Inc.
11q deletions in human colorectal carcinomas: Cytogenetics and restriction fragment length polymorphism analysis
Authors: Keldysh Peter L. , Dragani Tommaso A. , Fleischman Elena W. , Konstantinova Liliya N. , Perevoschikov Alexander G. , Pierotti Marco A. , Porta Giuseppe Della , Kopnin Boris P.
Published: February 2007

Deletions and/or allelic losses of a portion of the long arm of chromosome 11 were discovered by cytogenetic and restriction fragment length polymorphism analyses in 23 of 39 (59%) informative cases of colorectal carcinoma. By comparing the patterns of loss of heterozygosity and chromosome rearrangements in different patients, we could map a common target region to 11q22‐23. This region may contain a tumor suppressor gene, the inactivation of which may be involved in the development of tumors of the large intestine. The subgroup of malignancies with 11q alterations seemed to be enriched by tumors that were located in the rectum, that were Dukes' stage A, and that were well differentiated and mucin producing.© 1993 Wiley‐Liss,
Chromosome analysis of 20 breast carcinomas: Cytogenetic multiclonality and karyotypic‐pathologic correlations
Authors: Pandis Nikos , Heim Sverre , Bardi Georgia , Idvall Ingrid , Mandahl Nils , Mitelman Felix
Published: February 2007

Short‐term cultures from 20 breast carcinomas were analyzed cytogenetically. A normal female chromosome complement was found in 4 cases. Clonal chromosome aberrations were detected in 16 tumors. In 10 tumors, multiple cytogenetic clones were found; in 2 cancers the clones were related, reflecting clonal evolution, but in the remaining 8 tumors the clones were cytogenetically unrelated, indicating clonal heterogeneity in the origin of the tumor parenchyma. Correlation analysis between karyotypic and pathologic parameters indicated that cases with complex karyotypes and/or cytogenetically unrelated clones, when compared with cases with a single simple karyotypic abnormality, were generally of higher histologic malignancy grade, had more mitoses in the histologic sections, and also more often had carcinoma in situ lesions in the same breast. © 1993 Wiley‐Liss, Inc.
No germline TP53 mutations detected in familial and bilateral testicular cancer
Authors: Heimdal Ketil , Lothe Ragnhild A. , Lystad Sigrid , Holm Ruth , Fosså Sophie D. , Børresen Anne‐Lise
Published: February 2007

Mutations in the TP53 gene are considered to be among the most common genetic alterations in human cancers. Both somatic and germline mutations have been found. Using potymerase chain reaction (PCR), constant denaturant gel electrophoresis (CDGE), and denaturing gradient gel electrophoresis (DGGE), we have examined 32 patients with bilateral and familial germ cell tumors (GCT) and two patients with sporadic GCT for germline mutations within the conserved regions of the gene. In addition, 15 tumors were screened for somatic mutations and analyzed for loss of heterozygocity (LOH) at the TP53 locus. Twelve tumors were analyzed for expression of TP53 via immunohistochemistry. Neither germline nor somatic TP53 mutations were deteeted. LOH was observed in one of five informative cases. No tumors showed increased expression of TP53 protein. These results indicate that alterations in the TP53 gene are not important for the predisposition to and development of GCT. © 1993 Wiley‐Liss, Inc.
Telomeric associations and loss of telomeric DNA repeats in renal tumors
Authors: Holzmann Karlheinz , Blin Nikolaus , Welter Cornelius , Zang Klaus D. , Seitz Gerhard , Henn Wolfram
Published: February 2007

In a series of cytogenetically analyzed renal tumors of different histological types (chromophobe carcinoma, clear‐cell carcinoma, chromophilic carcinoma, and oncocytoma) and normal renal tissue, the length of the telomeric DNA repeats was assessed using a (TTAGGG)3 oligonucleotide probe. A strong correlation was noted between pronounced telomere shortening and the appearance of telomeric associations of chromosomes. These data suggest an etiologic role of the loss of telomeric DNA repeats in the formation of telomeric associations and a possible involvement of this mechanism in the pathogenesis of chromosome aberrations in human tumors. © 1993 Wiley‐Liss, Inc.
Recombination between separate MYC amplification structures in COLO320 cells
Authors: Vandevanter Donald R. , Yirdaw Getachew
Published: February 2007

Cytogenetically visible gene amplification structures can consist of arrays of amplicons presumably formed by secondary “rearrangements” following amplicon formation. The structural evolution of gene amplification sites in tumor cells suggests that complex secondary structures may have some selective advantage in the tumor cell environment. Although secondary amplicon rearrangements are a hallmark of the gene amplification process, little is known about the mechanics of this process. COLO320 neuroendocrine tumor cells carry two different types of amplified MYC oncogene sequences, one type with an intact MYC gene and the other with a rearranged “chimeric” MYC gene. We have studied various clonal subpopulations of COLO320 cells and identified regions within and downstream of the MYC locus that are unique to each amplicon type. Using double‐label fluorescence in situ hybridization with DNA probes unique to each amplicon type, we have observed that both chromosomal and extrachromosomal MYC amplicon arrays in COLO320 cells frequently consist of heterogeneous mixtures of each MYC amplicon type. Our results suggest that the two MYC amplicon types of COLO320 cells were formed simultaneously but independently, and that double minute chromosomes observed in COLO320 cells were formed by intermolecular homologous recombination secondary to amplicon formation. © 1993 Wiley‐Liss, Inc.
Clonal chromosome aberrations in neurinomas
Authors: Bello M. Josefa , De Campos José M. , Kusak M. Elena , Vaquero Jesús , Sarasa José L. , Pestaña Angel , Rey Juan A.
Published: February 2007

Chromosome studies were performed after short‐term in vitro culture of 39 samples from neurinomas and two samples from malignant schwannomas. Clonal abnormalities involving chromosome 22 were observed in 23 cases, as the sole chromosomal deviation in 12 of them. In 11 samples, other clonal numerical and/or structural aberrations were detected in addition to loss of chromosome 22, either in the same cells or in cells other than those having monosomy 22. Within the group of neurinomas with no involvement of chromosome 22, there were again two cytogenetically distinctive subgroups: one with an abnormal karyotype, and the second with a normal chromosome complement. Our findings confirm that monosomy 22 is a characteristic feature of this type of neoplasm, but also suggest the existence of different cytogenetic subgroups of neurinomas. © 1993 Wiley‐Liss, Inc.
Mapping the breakpoint of a constitutional translocation on chromosome 22 in a patient with NF2
Authors: Arai Eiko , Tokino Takashi , Imai Takashi , Inazawa Johji , Ikeuchi Tatsuro , Tonomura Akira , Nakamura Yusuke
Published: February 2007

Neurofibromatosis type 2 (NF2) is an autosomal dominant disorder characterized by development of bilateral acoustic neurinomas and increased incidence of meningiomas. Frequent losses of 1 allele of chromosome 22 in neurinomas and meningiomas has indicated that the gene responsible for NF2 functions as a tumor suppressor. Although the NF2 gene has been mapped within a 13 cM region between D22S1 and D22S28 by linkage analysis, its location with respect to D22S15 is uncertain. We previously reported an NF2 patient with a constitutional balanced translocation t(4;22) (q12;q12.2); the NF2 gene is probably disrupted at the breakpoint. To define the location of this breakpoint on chromosome 22, we performed fluorescence in situ hybridization (FISH) with DNA markers in the NF2 region and determined the physical order of 5 loci: D22S1‐NF2‐LIF‐D22S15‐D22S32. © 1993 Wiley‐Liss, Inc.
Translocation t(12;22)(q13;q12.2–12.3) in a clear cell sarcoma of tendons and aponeuroses
Authors: Mrózek Krzysztof , Karakousis Constantine P. , Perez‐Mesa Carlos , Bloomfield Clara D.
Published: February 2007

Cytogenetic analysis of a short‐term culture from a clear cell sarcoma revealed a complex karyotype with the mainline of 49,XY,t(7;18)(p11.2;q21.3), + der(7)t(7;18)(p11.2;q21.3), + 8, + der(8;17)(q10;q10),t(12;22)(q13;q12.2–12.3),add(13)(p13). An apparently identical translocation t(12;22) has been described recently in four clear cell sarcomas, indicating that this constitutes a primary cytogenetic change specific for this type of tumor. In our case, the breakpoint on chromosome 22 could be assigned to band 22q12.2 or 22q12.3. Together with the present case, trisomy or tetrasomy 8 has been found in six of nine clear cell sarcomas, suggesting that, as in Ewing's sarcoma and myxoid liposarcoma, trisomy/tetrasomy 8 represents a nonrandom secondary aberration. We conclude that the finding of the specific translocation t(12;22) may prove to be an important marker in the differential diagnosis of clear cell sarcoma from some other soft tissue sarcomas and malignant melanoma. © 1993 Wiley‐Liss, Inc.
t(11;18)(q21;q21) may delineate a spectrum of diffuse small B‐cell lymphoma with extranodal involvement
Authors: Leroux Dominique , Seité Paule , Hillion Josette , le Marc'hadour François , Pégourié‐Bandelier Brigitte , Jacob Marie‐Christine , Larsen Christian‐Jacques , Sotto Jean‐Jacques
Published: February 2007

We describe a patient with stage IV non‐Hodgkin's lymphoma (NHL) and a t(11;18)(q21;q21) translocation. He presented with a gastric small B‐cell lymphocytic lymphoma, expressing IgAL immunoglobulins without expression of CD10, CD5, and CD23 antigens. The lymphoma was the final development of a 6‐year history of a monoclonal IgAL increase complicated by severe renal failure due to membranoproliferative glomerulonephritis. The clinical, histological, immunologic, and cytogenetic features of this patient are very similar to those observed in the five other patients with t(11;18) reported to date. This translocation therefore seems to delineate a new subtype of diffuse small B‐cell lymphoma with involvement of mucosal sites. Involvement of the BCL2 oncogene on 18q21 could not be detected using molecular techniques with 5′ as well as 3′ BCL2 probes, indicating that other, so far unknown, genes relevant to lymphoid differentiation could be located in 18q21 and 11q21. © 1993 Wiley‐Liss, Inc.
Cytogenetic studies in sporadic and multiple endocrine neoplasia type 1‐associated pituitary adenomas
Authors: Papi Laura , Baldassarri Gabriella , Montali Enrico , Bigozzi Umberto , Ammannati Franco , Brandi Maria Luisa
Published: February 2007

Four sporadic and two multiple endocrine neoplasia type 1‐associated pituitary adenomas were studied. A t(1;21)(q32;22) was discovered in one of the two hereditary tumors. © 1993 Wiley‐Liss, Inc.
Frequent loss of 11p13 and 11p15 loci in male germ cell tumours
Authors: Lothe Ragnhild A. , Hastie Nick , Heimdal Ketil , Fosså Sophie D. , Stenwig Anna Elisabeth , Børresen Anne‐Lise
Published: February 2007

Deletions within the short arm of the human chromosome 11 have been found to be involved in the genesis of several tumours, including different urogenital neoplasms. We have studied 31 male germ cell tumours (19 seminomas and 12 nonseminomas), and observed loss of heterozygosity at 11p loci in 40% (12/30) of these tumours [35% (9/26) at 11p13 and 31% (8/26) at 11p15]. Our data suggest that inactivation of one or more tumour suppressor genes on 11p are involved in the genesis of testicular cancer. In addition, identification of the parental origin of the allelic losses revealed a paternal loss in six patients and a maternal loss in one case. © 1993 Wiley‐Liss, Inc.
Use of the single‐strand conformation polymorphism technique to detect loss of heterozygosity in neuroblastoma
Authors: White Peter S. , Kaufman Bruce A. , Marshall Helen N. , Brodeur Garrett M.
Published: February 2007

Human neuroblastomas are characterized by cytogenetic and molecular analysis as frequently containing deletions of distal 1p. Loss of heterozygosity (LOH) studies have localized a region of shared deletion to 1p35–36.1. Using the single‐strand conformation polymorphism (SSCP) technique, we developed polymorphic assays for two genes, the amiloride‐sensitive Na+/H+ antiporter (APNH) and tumor necrosis factor receptor 2 (TNFR2) genes, which map to this region. We used these SSCPs to detect LOH in a panel of neuroblastomas. Allelic loss was readily detected in 8 of 39 informative tumors. The SSCP‐derived LOH results were consistent with LOH results generated from a set of distal 1p probes that identify restriction fragment length polymorphisms (RFLPs). The APNH locus could be excluded from the region of consistent deletion, but the TNFR2 locus could not be excluded. We conclude that the SSCP technique is a precise and efficient method for detecting LOH in human neoplasia. © 1993 Wiley‐Liss, Inc.
In situ hybridisation analysis of a homogeneously staining region at 11q23–24 in an acute myeloid leukaemia (M5) using yeast artificial chromosomes
Authors: Nacheva Elisabeth , Kearney Lyndal , Bower Mark , Chaplin Tracy , Douek Edward , Das Soma , Young Bryan D.
Published: February 2007

An example of a homogeneously staining region (hsr), occurring in an acute myeloid leukaemia (M5) on chromosome 11 in the region of bands q23–q24, has been analysed. In situ hybridisation using yeast artificial chromosome (YAC) DNA demonstrated that the amplification did not include the CD3 gene cluster and did not affect the human trithorax gene known to be disrupted by translocations at 11q23. In contrast, the amplification was shown to include the sequence D11S543 which has been previously mapped to chromosome band 11q24. High resolution analysis using confocal microscopy allowed the individual amplicons to be visualised, and it was shown that the hsr consisted of an 8‐fold amplification of the region surrounding the probe D11S543. From previous estimates of human chromosome size it was possible to calculate that the hsr was composed of amplicons approximately 10 megabases in length. It was concluded that the region amplified did not extend as far as the translocation breakpoints occurring at 11q23 in acute leukaemias. © 1993 Wiley‐Liss, Inc.
Do terminal deletions of 11q23 exist? Identification of undetected translocations with fluorescence in situ hybridization
Authors: Kobayashi Hirofumi , Espinosa Rafael , Thirman Michael J. , Fernald Anthony A. , Shannon Kevin , Diaz Manuel O. , le Beau Michelle M. , Rowley Janet D.
Published: February 2007

Fluorescence in situ hybridization (FISH) was performed on bone marrow or peripheral blood cells thought to contain a del(11)(q23q25) from four patients who had acute leukemia or myelodysplasia. Cells from all patients were shown to contain translocations that involved chromosome 6 in three of them. Our data suggest that a large proportion of presumptive del(11)(q23) or del(11)(q23q25) chromosomes may represent previously unidentified translocations that can be detected by FISH. © 1993 Wiley‐Liss, Inc.
Chromosomal radiosensitivity at intrachromosomal telomeric sites
Authors: Alvarez Luis , Evans James W. , Wilks Rebecah , Lucas Joe N. , Brown J. Martin , Giaccia Amato J.
Published: February 2007

Telomeric DNA is composed of highly conserved sequences which are present at the termini of chromosomes as well as at intrachromosomal locations. Here, we studied a Chinese hamster ovary (CHO) cell line, BL‐10, with highly stable amplified telomeric DNA at the termini as well as at intrachromosomal locations. We show that intrachromosomal or interstitial telomeric sites in this cell line and in another CHO cell line, HA‐1, are radiosensitive in that they are more prone to breakage than would be expected based on the percentage of the genome composed of telomeric sequences. The frequency of breakage at interstitial telomeric sites is 4.3 to 8.3 times higher than that in the CHO genome overall. These conclusions are reached by both conventional cytogenetic analysis of two CHO cell lines which have the same survival rates after exposure to ionizing radiation, and by use of double fluorescence in situ hybridization (FISH) with a pan‐telomere‐specific probe and a CHO chromosome‐specific library in the same metaphase cells after irradiation. © 1993 Wiley‐Liss, Inc.
Detection of sex‐region Y (SRY) transcripts in human prostate adenocarcinoma and benign prostatic hypertrophy
Authors: Tricoli James V. , Yao Joyce L. , D'Souza Sharon A. , Bracken R. Bruce
Published: February 2007

The human sex‐region Y (SRY) gene maps to Yp 11.3 and encodes a protein that shares significant sequence homology with a conserved DNA binding motif found in the nonhistone high‐mobility group (HMG) proteins. In the mouse, Sry is required for normal testicular development and is expressed in the developing male gonadal ridge as well as in the adult testis. In man, SRY expression has been observed in the adult testis, but not in other adult male tissues. We have analyzed samples from human prostate adenocarcinoma and benign prostatic hypertrophy (BPH) for the expression of the SRY gene. We found expression of SRY in 60% of malignant prostate tumors and in three of six samples of BPH. We did not find expression in male or female colon mucosa, or in tissue from a cystic ovary. Malignant and atrophic testicular tissue both contained SRY transcript and served as positive controls in these experiments. We also found SRY transcript in the DU‐145 prostate adenocarcinoma cell line. Interestingly, SRY expression is absent in the Tera‐2 teratocarcinoma cell line. The potential for the SRY gene product to bind HMG core response elements in vitro suggests that SRY could participate in the cascade of gene regulatory events that result in aberrant cell growth or malignancy. © 1993 Wiley‐Liss, Inc.
Oligoclonal B‐cell leukemia characterized by spontaneous cell division and telomere association
Authors: Crossen Peter E. , Tully Sandra M. , Benjes Suzanne M. , Hollings Peter E. , Beard Michael E. J. , Nimmo Joy C. , Morrison Mary J.
Published: February 2007

Cytogenetic analysis of unstimulated cultures from a female patient with chronic B‐cell leukemia (CLL) revealed three cytogenetically distinct clones, suggesting that the patient's leukemia was oligoclonal. Immunoglobulin heavy chain gene rearrangement studies revealed 1 germline and 4 rearranged bands, indicative of an oligoclonal leukemc population. Further evidence of oligoclonality was provided by X‐linked RFLP studies. This is the first report of oligoclonality in CLL demonstrated by cytogenetic, immunoglobulin gene rearrangement, and X‐chromosome inactivation studies. In addition to oligoclonality, the patient's leukemk cells exhibited telomere association, a Robertsonian translocation, and clonal evolution, suggesting an underlying genomic instability. © 1993 Wiley‐Liss, Inc.
Localization of two tyrosine kinase receptor genes with respect to the 5q35 chromosomal breakpoint of Ki‐1 lymphoma cell lines
Authors: Pébusque Marie‐Josèphe , Lafage Marina , Galland Franck , Simonetti Jacqueline , Armstrong Elina , Rimokh Ruth , Birnbaum Daniel
Published: February 2007

The consistency of the breakpoint on chromosome 5 at band 5q35 occurring in Ki‐1 non‐Hodgkin's lymphomas is highly suggestive of the involvement of a locally altered gene in this disease. In this study, we analyzed the potential involvement, in the translocation, of two receptor tyrosine kinase genes and putative oncogenes, FLT4 and FGFR4, previously localized near this breakpoint. Fluorescence in situ chromosomal hybridization allowed us to refine their localization to sub‐band 5q35.3 and to show that both genes are translocated to the derivative chromosomes in Ki‐1 cell lines containing either a t(2;5) or a t(3;5). Pulsed‐field gel electrophoresis showed that the FLT4 and FGFR4 genes are not physically linked, nor are they altered by the translocation. Finally, Northern blot analysis showed that neither FLT4 nor FGFR4 is expressed in the Ki‐1 cell lines, suggesting that they are not implicated in the genesis of Ki‐1 lymphomas. © 1993 Wiley‐Linc, Inc.
Y chromosome loss in esophageal carcinoma: An in situ hybridization study
Authors: Hunter Stephen , Gramlich Terry , Abbott Karen , Varma Vijay
Published: February 2007

Carcinoma of the esophagus shows a strong male predominance and other epidemiologic differences from cancers arising at other sites. In this study, the prevalence of Y chromosome loss in 29 carcinomas of the esophagus and 53 carcinomas arising elsewhere in the aerodigestive tract was assessed by in situ hybridization of formalin‐fixed paraffin‐embedded tissue sections. Absence of the Y chromosome was defined as (1) negative staining for Y in neoplastic cells with positive staining for Y in immediately adjacent nonneoplastic epithelial and stromal cells, (2) positive staining of neoplastic cells with control probes for chromosomes X and 17, and (3) similar results at different stringencies and levels of protein digestion. According to these criteria, absence of the Y chromosome was observed in 13 of 14 (93%) adenocarcinomas of the esophagus, 8 of 13 (62%) squamous cell carcinomas of the esophagus, and 5 of 53 (9%) carcinomas arising in other sites. For the neoplasms examined, Y chromosome deletion was strongly and selectively associated with carcinomas, particularly adenocarcinomas, of the esophagus (P < .0001). These findings suggest that Y chromosome loss may be pathogenetically significant in these neoplasms. © 1993 Wiley‐Liss, Inc.
Chromosome 10 allelic loss in malignant melanoma
Authors: Isshiki Koichi , Elder David E. , Guerry Dupont , Linnenbach Alban J.
Published: February 2007

The involvement of tumor suppressor genes in the progression of melanoma has been suggested by the frequent deletion of specific regions of the genome in melanoma. In this study, a panel of 18 surgically removed melanomas from 15 patients was analyzed for loss of heterozygosity (LOH) at 10 polymorphic loci on chromosome 10. LOH was observed in 7 (50%) of 14 informative patients. LOH data suggested that melanomas from 5 patients had lost entire copies of chromosome 10, and that melanomas from 2 patients had lost copies of 10q. In contrast, LOH was not observed on chromosome 15, 20, or 21. These results are consistent with previous cytogenetic observations and provide indirect evidence that there is a tumor suppressor gene on the long arm of chromosome 10 which is relevant to melanoma development. © 1993 Wiley‐Liss, Inc.
Power of the MAC (Morphology‐Antibody‐Chromosomes) method in distinguishing reactive and clonal cells: Report of a patient with acute lymphatic leukemia, eosinophilia, and t(5;14)
Authors: Knuutila Sakari , Alitalo Riitta , Ruutu Tapani
Published: February 2007

We present a patient with acute lymphatic leukemia, eosinophilia, and a 5;14‐translocation, a rare but well‐documented condition. In order to clarify whether granulocytes were involved in the disease, we applied the MAC (Morphology‐Antibody‐Chromosomes) technique to samples of the bone marrow and, during a central nervous system relapse, to those of the cerebrospinal fluid. The karyotype of the blast cells was 47,XY,+X,t(5;14)(q31;q32),i(7)(q10). Interphase cytogenetic study by in situ hybridization with an X‐specific alphoid probe revealed the abnormality in CD10, CD19, and TdT (terminal deoxynucleotidyl transferase) positive lymphoid cells, whereas CD13 positive, Sudan black B positive, eosinophilic, and basophilic granulocytes as well as monocytes and small lymphocytes did not have the abnormality. Our results show that the eosinophilic and basophilic granulocytes in this subtype of acute leukemia do not belong to the malignant clone but are reactive. This study also confirmed the usefulness of the MAC technique in distinguishing neoplastic and reactive cells in malignancy.© 1993 Wiley‐Liss, Inc.