bluuebunny/crossref_metadata_2025 huggingface dataset:
Co‐amplification of the gene for parathyroid hormone‐related protein (PTHRP) and KRAS2 in a human lung cancer cell line
Authors: Rudduck Christina , Duncan Lisa , Center Rob , Garson O. Margaret
Published: February 2007

Parathyroid hormone‐related protein (PTHRP) is expressed in a large number of tumors and is the mediator of parathyroid hormone‐like effects seen in humoral hypercalcemia of malignancy. The gene coding for PTHRP has been localised to the short arm of chromosome 12. This is at the same region as the oncogene KRAS2, and amplification of KRAS2 has previously been found in human lung cancer. The BEN cell line which is known to express PTHRP was established from a patient who had squamous cell carcinoma of the lung with hypercalcemia. Cytogenetic analysis of the BEN cell line revealed a very complex karyotype with many marker chromosomes. Chromosomal in situ hybridization with biotinylated DNA probes visualized by a biotin‐streptavidin‐polyalkaline‐phosphatase complex was used to analyse two dicentric marker chromosomes containing homogeneously staining regions (hsr) in BEN. The hsr were found to contain amplified PTHRP and KRAS2 at levels of 30‐fold and 14‐fold per cell, respectively. The higher level of amplification of the PTHRP gene would suggest that PTHRP is the target gene of amplification in the amplicon. This is the first report of gene amplification of PTHRP and in addition its co‐amplification with KRAS2. © 1993 Wiley‐Liss, Inc.
FGFRI and PLAT genes and DNA amplification at 8p 12 in breast and ovarian cancers
Authors: Theillet Charles , Adelaide José , Louason Geneviève , Bonnet‐Dorion Françoise , Jacquemier Jocelyne , Adnane Jalila , Longy Michel , Katsaros Dionisi , Sismondi Piero , Gaudray Patrick , Birnbaum Daniel
Published: February 2007

Several chromosomal regions are found to be consistently amplified in human breast cancers. For two of these regions, 8p 12 and 10q26, we previously reported the amplification of genes encoding FGF receptors, FGFR1/FLG and FGFR2/BEK, in about 12% of breast tumors. The PLAT gene, encoding the tissue‐type plasminogen activator, is also located close to or within the 8p 12 region. In the present study, we show that both FGFR1 and PLAT can be amplified in breast as well as ovarian carcinomas. FGFR1 amplification was detected in 14.5% of breast and 7.8% of ovarian tumors, whereas PLAT was found to be amplified in 15.6% and 19.4% of the tumors, respectively. Each gene could be amplified independently of the other. These data raised the question of which gene is selected for amplification at 8p 12. In most cases, the levels of expression of FGFR1 and PLAT in breast tumors were comparable to their level of expression in normal mammary tissue. However, FGFR1 was expressed above the normal level in a certain number of cases. This gene could be a good candidate as “driver” of the 8p 12 amplification, but it cannot account for all complex molecular events taking place in this region. © 1993 Wiley‐Liss, Inc.
Chromosome painting as a supplement to cytogenetic banding analysis in non‐Hodgkin's lymphoma
Authors: Bajalica Svetlana , Sørensen Anne‐Grethe , Pedersen Niels Tinggaard , Heim Sverre , Brøndum‐Nielsen Karen
Published: February 2007

Chromosomal in situ suppression (CISS) hybridization with biotin labeled chromosome‐specific libraries was performed on short‐term cultures from five cases of non‐Hodgkin's lymphoma (NHL). The painting analysis proceeded in three stages. First‐stage CISS hybridization was done with libraries specific for chromosomes that seemed to be lost or rearranged as judged by banding analysis. Second‐stage CISS included hybridization with probes specific for chromosomes that, because of banding pattern similarities, were considered to be likely candidates to have contributed unidentified chromatin blocks in the abnormal karyotype. The third and final stage was a confirmation hybridization with a library specific for the chromosome that, at the stage two analysis, was found to have donated the previously unknown chromosomal segment. The aberrant chromosomes were often more complex than the banding analysis had led us to believe. Among the rearrangements whose nature was determined by CISS hybridization were two add(1)(p36) which, in both cases, were shown to be a der(1)t(1;2)(p36;q31). This study illustrates the potential use of chromosome painting in resolving karyotypic uncertainties in NHL, and it shows that new cytogenetic subgroups may emerge when classical banding analysis is supplemented with fluorescence in situ hybridization techniques. © 1993 Wiley‐Liss, Inc.
Tissue culture loss of aneuploid cells from carcinomas of the prostate
Authors: König Josée J. , Teubel Wilma , Van Dongen Jan Willem , Hagemeijer Anne , Romijn Johannes C. , Schröder Fritz H.
Published: February 2007

The frequency of aneuploid cells in cultured prostate carcinoma specimens was investigated. Ploidy distribution of the original tissue was established by flow cytometry (FCM). Fluorescence in situ hybridization (FISH) of chromosome I was applied to directly isolated and cultured cells to investigate whether any modifications in the ploidy distribution of chromosome I took place during tissue culture. In six tumor specimens that were diploid by FCM and FISH, no differences were found in the ploidy distribution of chromosome I before and after tissue culture. In eight tumors that were aneuploid by FISH, the percentage of aneuploid nuclei was significantly reduced from 28.0 ± 15.0 (range 13ndash;59%) in uncultured cells to 9.1 ± 4.4 (range 4ndash;18%) after tissue culture. The reduction of aneuploid nuclei ranged from 44 to 85%, which means that the majority of the aneuploid cell populations that were observed in the original specimens were undetectable in cultured samples. This suggests a preferential growth of normal epithelial cells. The data presented can explain the high percentage of diploid karyotypes usually found in short‐term cultured prostate carcinoma specimens. © 1993 Wiley‐Liss, Inc.
Non‐random integration of epstein‐barr virus in lymphoblastoid cell lines
Authors: Lestou Valia S. , De Braekeleer Marc , Strehl Sabine , Ott German , Gadner Helmut , Ambros Peter F.
Published: February 2007

In order to examine the role of Epstein‐Barr virus (EBV) in the immortalization of human 6 lymphocytes and in the pathogenesis of lymphoid malignancies, we investigated whether the EBV integration into the human genome is randomly distributed or whether the virus integrates preferentially at certain sites. Twelve in vitro immortalized human lymphoblastoid cell lines (LCLs), two in vivo infected LCLs, and one Burkitt's lymphoma cell line (EB2) were examined by non‐radioactive in situ hybridization (ISH) with a biotinylated EBV probe. Recurrent hybridization sites were detected in all 15 cell lines. The chromosomes frequently carrying the EBV genome were chromosomes 1, 2, 4, and 5. In more than 70 chromosomal bands, a greater number of integration sites than expected was found (p < 0.05). Approximately half of these bands were involved in the majority of the cell lines (for example, 1p31, 1q43, 2p22, 3q28, 4q13, 5p14, 5q12, and 11p15) whereby band 5p14 was involved in all LCLs analyzed. Virtually no viral integrations were found on the sex chromosomes (X, Y). The majority of the EBV integrations was found in G‐band‐positive material (p < 0.0001). Thus, our findings clearly show that EBV integrates into the human genome in a non‐random manner. © 1993 Wiley‐Liss, Inc.
Cloning and sequencing of a t(14;19) breakpoint that involves the Cμ switch region
Authors: Crossen Peter E. , Kennedy Martin A. , Heaton David C. , Morrison Mary J.
Published: February 2007

The t(14;19) is a recurring translocation found in a small number of cases of chronic B‐cell leukemia (CLL). We have cloned and sequenced the breakpoint in a patient with a t(14;19) and shown that the breakpoint on chromosome 14 occurred in the Cμ switch region, and that the breakpoint on chromosome 19 occurred in the 5′ untranslated region of the BCL3 gene. This is in contrast to all the other reported cases with a t(14;19) in which the breakpoints on chromosome 14 occurred in the Cαl or Cα2 switch region, and the breakpoints on chromosome 19 occurred upstream of the BCL3 gene. Our results further emphasize the importance of the switch region in the t(14;19) translocation. © 1993 Wiley‐Liss, Inc.
Numerical aberrations, including trisomy 22 as the sole anomaly, are recurrent in follicular thyroid adenomas
Authors: Antonini Patrick , Lévy Nicolas , Caillou Bernard , Vénuat Anne‐Marie , Schlumberger Martin , Parmentier Claude , Bernheim Alain
Published: February 2007

Short‐term cultures from 38 follicular thyroid adenomas revealed clonal numerical and/or structural chromosomal changes in 8 tumors, nonclonal changes in I tumor, and only normal karyotypes in 29 tumors. Three cases had trisomy 22 as the sole anomaly. Two cases had a combination of trisomies for chromosomes 5, 7, 9, 12, and 16. © 1993 Wiley‐Liss, Inc.
Low frequency of mutations in the WT1 coding region in Wilms' tumor
Authors: Brown Keith W. , Wilmore Helen P. , Watson Joanne E. , Mott Martin G. , Berry P. Jeremy , Maitland Norman J.
Published: February 2007

A series of twenty unselected Wilms′ tumors were analysed for alterations in the WT1 tumor suppressor gene. The entire coding region of WT1 was amplified by RNA‐PCR, and then screened for mutations by single‐strand conformational polymorphism analysis (SSCP). This method was shown to be capable of detecting point mutations in the WT1 gene, by using an experimentally produced mutation. A single mutation, a 226 bp intragenic deletion, was detected in a tumor from a patient with the WAGR syndrome. These results suggest that alterations in the WT1 gene may be involved in only a subset of Wilms′ tumors, and that other loci need to be investigated as potential suppressor genes in sporadic Wilms′ tumors. © 1993 Wiley‐Liss, Inc.
Expanded range of 11q13 breakpoints with differing patterns of cyclin D1 expression in B‐cell malignancies
Authors: Raynaud Sophie D. , Bekri Soumeya , Leroux Dominique , Grosgeorge Josiane , Klein Bernard , Bastard Christian , Gaudray Patrick , Simon Marie‐Pierre
Published: February 2007

We have analyzed the BCL1 locus in a series of 24 B‐cell tumors and cell lines with rearrangements of 11q13 (mostly t(11;14)(q13;q32) translocations). Using Southern hybridization and/or fluorescence in situ hybridization (FISH) on metaphase chromosomes, we have not only confirmed the scattering of the breakpoints between the BCL1 locus and the cyclin DI gene (CCND1), but also shown that some of the breakpoints could be as far as 500 kb on either side of the latter. Expression of CCND1 was not restricted to cases with t(11;14)(q13;q32), but was also associated with other 11q13 rearrangements, such as a t(8;11)(p22;q13). Whatever the alteration at 11q13, a correlation was observed between the expression of CCND1 and the presence of a breakpoint within 150 kb upstream of the gene. On the contrary, three samples, including a bona fide t(11;14) translocation and two cases with breakpoints located outside the BCL1‐CCND1 area, did not exhibit detectable levels of CCND1 transcripts. Our results raise the possibility that several discrete molecular events can take place at 11q13 in B‐cell malignancies. © 1993 Wiley‐Liss, Inc.
Three non‐overlapping regions of chromosome arm 11p allele loss identified in infantile tumors of adrenal and liver
Authors: Byrne Jennifer A. , Simms Lisa A. , Little Melissa H. , Algar Elizabeth M. , Smith Peter J.
Published: February 2007

Tumor and constitutional chromosome arm 11p genotypes were compared in 6 hepatoblastoma (HB) patients and 2 adrenal adenoma (AA) patients, with one HB patient and both AA patients displaying clinical features associated with the Beckwith‐Wiedemann syndrome (BWS). Using up to 14 chromosome 11 polymorphic markers, loss of constitutional heterozygosity (LOH) was demonstrated in both AA patients and in 4 of 6 HB patients. This identified three distinct and non‐overlapping regions of 11p within which LOH occurred, which were defined as lying distal to the gamma‐globin locus (11p15.5), proximal to the gamma‐globin locus but distal to 11p13 (LOH being detected at 11p15.1), and restricted to the 11p13 region. Specific LOH within each 11p15 region was observed in HB, and this represents the first demonstration by a single study of LOH clearly affecting separate regions of chromosome band 11p15 in a particular tumor type. One AA showed LOH restricted to 11p13 loci, implicating the involvement of the WT1 gene. The second AA patient presented with genitourinary abnormalities and we therefore examined sequences coding for 3 zinc finger domains of WT1 in both AAs. No point mutations were identified in sequence from either patient. Nonetheless our results indicate that 3 separate 11p loci may be significant in the development of tumors which arise in association with BWS. © 1993 Wiley‐Liss, Inc.
Direct visualization of the transposed ABL gene in a duplicated masked Ph chromosome
Authors: Macera M. J. , Szabo P. , Lin J. H. , Desalvo A. T. , Shah H. O. , Verma R. S.
Published: February 2007

In a small percentage of cases of chronic myelogenous leukemia (CML), where the Ph chromosome is masked because of highly complex translocations and sub‐microscopic rearrangements, precise identification of chromosomal aberrations by routine banding techniques has been difficult. We report on a new case of CML in which a single copy of a masked Ph chromosome was duplicated during blast crisis, i.e., the karyotype was 47,XY, dir ins(22;9)(q11;q34.1q34.2),t(1;22) (q21;q11), + der (22)t(1;22)(q21;q11). The chromosome in situ suppression hybridization (CISS) technique with whole chromosome 1 and 22 specific painting probes demonstrated that 22q11‐qter had been translocated to lq21, whereas 22q11 was the recipient of Iq21‐qter. Furthermore, a cosmid probe identified the location of the ABL gene on only one chromosome 9 (band q34). The other ABL gene could be detected on both derivative chromosomes 22 at band q11 which was flanked by the translocated part of the long arm of chromosome I, thus providing direct visualization of the ABL insertion in a double masked Ph chromosome. A breakpoint within the 5.8 kb major breakpoint cluster [M‐BCR] region was shown by Southern blotting. © 1993 Wiley‐Linc, Inc.
Rearrangement of 12q14‐15 in pulmonary chondroid hamartoma
Authors: Cin Paola Dal , Kools Patrick , De Jonge Inge , Moerman Phillippe , Van De Ven Wim , Van Den Berghe Herman
Published: February 2007

Cytogenetic analysis of a pulmonary chondroid hamartoma showed an inv(12)(p13q14‐15) as the sole abnormality. This finding together with previously reported data is an indication that the 12q14‐15 region may be nonrandomly involved in the pathogenesis of this tumor type. © 1993 Wiley‐Liss, Inc.
Mapping of the 19p13 breakpoint in an ovarian carcinoma between the INSR and TCF3 Loci
Authors: Åman Pierre , Pejovic Tanja , Wennborg Anders , Heim Sverre , Mitelman Felix
Published: February 2007

Chromosome rearrangements involving band 19p13 have been described in about half of all ovarian carcinomas. Four ovarian carcinomas with translocations of 19p13 were investigated with 11 DNA probes for markers localized to this band. All markers exhibited normal restriction patterns, suggesting that they were not rearranged. The 19p13 breakpoint of one tumor was mapped to a location between the INSR and the TCF3 loci. © 1993 Wiley‐Liss, Inc.
BCNU‐resistant human glioma cells with over‐representation of chromosomes 7 and 22 demonstrate increased copy number and expression of platelet‐derived growth factor genes
Authors: Scheck Adrienne C. , Mehta Bipin M. , Beikman Melanie K. , Shapiro Joan Rankin
Published: February 2007

We used standard karyotypic analyses of first‐division cells to identify a subpopulation of cells in primary malignant gliomas with over‐representation of chromosomes 7 and 22. These cells are a minor subpopulation in the primary tumor but become the dominant population after treatment in vitro of the cells with the chemotherapeutic agent 1,3‐bis(2‐chloroethyl)‐1‐nitrosourea (BCNU). The selection for a cell with this specific karyotypic abnormality suggests that these chromosomes contain genes important to the growth of BCNU‐resistant cells. Southern blot hybridization analyses demonstrate an increased copy number of the genes encoding platelet‐derived growth factor (PDGF) A‐chain and B‐chain, which have been mapped to chromosomes 7 and 22, respectively. Reverse transcription followed by polymerase chain reaction (RT‐PCR) analysis demonstrates increased expression of these genes. In addition, these cells secrete a mitogenic factor that stimulates 3H‐thymidine uptake in NIH 3T3 cells. This factor is sensitive to anti‐PDGF antibodies and β‐mercaptoethanol, but not to anti‐EGF antibodies. These data suggest that autocrine and/or paracrine mechanisms occur in human malignant gliomas, and that over‐expression of PDGF may play a role in the growth of BCNU‐resistant cells in these tumors. © 1993 Wiley‐Liss, Inc.
Extrachromosomal gene amplification in acute myeloid leukemia; Characterization by metaphase analysis, comparative genomic hybridization, and semi‐quantitative PCR
Authors: Mohamed A. N. , Macoska J. A. , Kallioniemi A. , Kallioniemi O.‐P. , Waldman F. , Ratanatharathorn V. , Wolman S. R.
Published: February 2007

A case of acute myeloid leukemia (M‐3) with complex karyotypic aberrations and double minute (dmin) chromosomes is presented. The patient had no history of prior exposure to mutagenic or carcinogenic agents or of other malignancies. She died from CNS involvement six weeks after the initial diagnosis. We used comparative genomic hybridization to identify the amplified sequences presumed to represent the dmin of the leukemic cells; the tumor/normal ratios indicated increased signal intensity at 8q24. This localization prompted investigation by semi‐quantitative PCR that revealed amplification of the MYC oncogene. The extent of chromosome aberrations and the oncogene amplification, both linked with poor prognosis, may relate to the rapid course of this patient's disease. © 1993 Wiley‐Liss, Inc.
Variant translocations of chromosome 22 in Ewing's sarcoma
Authors: Squire Jeremy , Zielenska Maria , Thorner Paul , Tennyson Shan , Weitzman Sheila , Pai K. Mohan , Yeger Herman , Ng Y‐Kwan , Weksberg Rosanna
Published: February 2007

Relatively few variant translocations have been reported in primary Ewing's sarcomas (ES). We report two new variant translocations, both of which involve chromosomal rearrangements of 22q12. Cytogenetic studies of tumor cells from a 12‐year‐old girl revealed a variant translocation, t(7;22)(p22;q12), the second example reported of a simple variant of the 22q12 reciprocal translocation in this type of sarcoma. The identity of this rearrangement was confirmed by in situ hybridization. In addition, a complex translocation was identified in a dysmorphic 15‐year‐old girl, t(4;11;22)(q21q24;q12). No previous cases of variant translocations in ES have involved band 7p22 or 4q21, and there are no previous reports of an association between congenital abnormalities and unusual karyotype abnormalities in ES. Both variant translocations conserve the junction on the der (22), providing additional cytogenetic evidence that the sequences on chromosome 22 are critical. © 1993 Wiley‐Liss, Inc.
Whole chromosome 17 loss in ovarian cancer
Authors: Tavassoli Mahvash , Ruhrberg Christiana , Beaumont Vicky , Reynolds Karina , Kirkham Nigel , Collins William P. , Farzaneh Farzin
Published: February 2007

Chromosomal deletions, associated with the loss of normal function of tumour suppressor genes, have been identified in a variety of both familial and sporadic human cancers. Although the molecular pathology of ovarian cancer is not understood, several studies have reported deletions in chromosome 17 in ovarian tumours. We have used 13 restriction site polymorphic, microsatellite, and variable number tandem repeat markers to make a detailed analysis of chromosome 17 deletions in 12 benign and 19 malignant ovarian tumours. Two benign and 11 malignant tumours were informative for at least one marker on each arm of the chromosome. Loss of heterozygosity (LOH) was detected in both arms (by all informative markers) in 5 malignant tumours from four women (three with the disease at FIGO stage la). In a further bilateral ovarian tumour a partial LOH affecting 17q22‐q25 was present in one ovary only. By contrast to a number of previous studies, none of the 19 malignant and 12 benign tumours showed ERBB2 (17q12ndash;22) amplification. The data presented show that the loss of a whole copy of chromosome 17 is a frequent and relatively early event in the development of some ovarian cancers. This suggests the possible involvement of multiple chromosome 17 loci in the pathogenesis of ovarian cancer. Equally plausible is that the loss of a whole chromosome copy could be the product of chromosomal instabilities induced by loss of the normal allele of tumour suppressors, such as TP53, located on this chromosome. © 1993 Wiley‐Liss, Inc.
Deletion of 3p25→pter in a primary follicular thyroid carcinoma and its metastasis
Authors: Roque Lúcia , Castedo Sérgio , Clode Ana , Soares Jorge
Published: February 2007

We report the cytogenetic analysis of a follicular thyroid carcinoma and its bone metastasis. Both lesions had identical chromosomal abnormalities, with a der(3)t(2;3)(q13;p25) as the most likely primary clonal alteration. Our findings corroborate previous observations of frequent 3p deletions in thyroid follicular carcinomas and suggest that the minimal chromosomal region of loss in these tumors is 3p25→pter. © 1993 Wiley‐Liss, Inc.
Molecular mapping of the chromosome 11 breakpoint of t(11;17)(q13;q21) in a t(11;14)(q13;q32)‐positive B non‐Hodgkin's lymphoma
Authors: Wlodarska Iwona , Schoenmakers Eric , Kas Koen , Merregaert Jozef , Lemahieu Vanessa , Weier Ulli , Berghe Herman Van Den , Van De Ven Wim J. M.
Published: February 2007

The FAU gene is the cellular homologue of the viral FOX sequences in the genome of the Finkel‐Biskis‐Reilly murine sarcoma virus (FBR‐MuSV); the viral FOX sequences have been shown to increase the transforming capacity of FBR‐MuSV in vitro. The human FAU gene has recently been isolated, characterized, and mapped to chromosome band 11q13. Here, we report results of fluorescence in situ hybridization (FISH) analysis which indicate that the FAU gene maps proximally to the putative oncogene BCL1 at 11q13. Furthermore, we identified a t(11;17)(q13;q21) translocation in tumor cells of a t(11;14)(q13;q32)‐positive B‐cell non‐Hodgkin's lymphoma patient by FISH analysis using a FAU containing cosmid clone as molecular probe and by double‐colour chromosome painting analysis using chromosome 11‐ and chromosome 17‐specific painting probes. The position of the chromosome 11 breakpoint of the t(11;17) translocation was pinpointed to a human DNA region around the FAU gene of about 40 kbp. © 1993 Wiley‐Liss, Inc.
Cytogenetic findings in malignant triton tumor
Authors: Travis Joni A. , Bridge Julia A. , Neff James R , Sandberg Avery A.
Published: February 2007

Malignant triton tumor is a rare histologic variant of malignant schwannoma that shows both neural and skeletal muscle differentiation. In this study, cytogenetic analysis of a recurrent malignant triton tumor of the forearm from a 26‐year‐old female and a primary paraspinal malignant triton tumor from a 27‐year‐old female revealed complex karyotypes displaying multiple numercial and structural abnormalities. Abnormalities shared by both tumors included three copies of chromosome 22 and structural rearrangements of chromosomes 2, 7, and 21 at identical or closely located breakpoints. Genes Chrom Cancer 9:1‐7 (1994). © 1994 Wiley‐Liss, Inc.
Loss of chromosome band 8q24 in sporadic osteocartilaginous exostoses
Authors: Mertens Fredrik , Helm Sverre , Mitelman Felix , Mandahl Nils , Rydholm Anders , Kreicbergs Andris , Willén Helena , Jonsson Kjell
Published: February 2007

We have karyotyped eight sporadic osteocartilaginous exostoses (OCE), a tumor type not characterized cytogenetically before. Five tumors had only normal karyotypes, whereas three displayed the following abnormal karyotypes: 46,XY,del(8)(q24.1); 46,XX,del(8)(q22), t(8;14)(q24. 1;q32); and 46,XY,der(8)t(1;8)(q21;q24), inv(12)(p1 1q13). All three aberrant cases thus had structural rearrangements leading to loss of the distal part of 8q. This is of particular interest because multiple OCE are part of the disease phenotype in patients with the autosomal dominant tricho‐rhino‐phalangeal syndrome type II (TRP II), many of whom have constitutional loss of genetic material from 8q24.1. We hypothesize that band 8q24.1 harbors a tumor suppressor gene, the homozygous inactivation of which is important in the genesis of both inherited and sporadic OCE. In the familial form, i.e., in TRP II, loss or functional inactivation of one allele is inherited and only the second mutation is due to a somatic event, whereas both mutations are somatic in the sporadic forms. This hypothesis can be tested by analysis of sporadic and inherited OCE for homozygous loss of 8q24 material with molecular genetic techniques. Genes Chrom Cancer 9:8‐12 (1994). ©1994 Wiley‐Liss, Inc.
Patterns of dna amplification at band q13 of chromosome 11 in human breast cancer
Authors: Karlseder Jan , Zeillinger Robert , Schneeberger Christian , Czerwenka Klaus , Speiser Paul , Kubista Ernst , Birnbaum Daniel , Gaudray Patrick , Theillet Charles
Published: February 2007

In an attempt to verify the nature of amplification events at band q13 on chromosome 11 we surveyed the amplification status of ten molecular markers specific for this region (GSTP, SEA, D11S97, D11S146, BCLI, PRAD1/CCND1, HST/FGF4, INT2/FGF3, EMS1, and D11S833E) in a panel of 389 primary breast carcinoma DNA samples. Eighty‐eight tumors (23%) showed at least one of these markers amplified, but in a majority of the cases amplification encompassed more than one of the tested loci. Our data confirm that amplicons at 11q13 can cover large portions of DNA and are consistent with the existence of several cores of amplification. One important core seems to be, as previously described, centered around PRAD1/CCND1; 57 tumors (14.7%) showed amplification at PRAD1/CCND1 either alone (one tumor) or along with amplification of BCL1 or INT2/FGF3. The level of amplification of PRAD1/CCND1 sometimes exceeded that of surrounding markers. Three additional amplification events occurring independently of amplification of PRAD1/CCND1 were also detected. Centromeric to BCL1, probes to D11S97, and D11S146 detected amplification in 60 tumors (15.4%) and were often the only amplified markers. Telomeric to INT2/FGF3, D11S833E was found amplified alone in ten tumors, and it was the most amplified marker in another six cases. At a shorter distance of INT2/FGF3, EMS1 was the only amplified marker in two tumors, with a level of amplification that could exceed that of PRAD1/CCND1 and D11S833E. Our data thus suggest the existence of four independent amplified regions within band 11q13 in breast cancer. Genes Chrom Cancer 9:42‐48 (1994). © 1994 Wiley‐Liss, Inc.
RARA and PML gene rearrangements in acute promyelocytic leukemia with complex translocations and atypical features
Authors: McKinney Christopher D. , Williams Michael E. , Golden Wendy L. , Gemma Nicholas W. , Swerdlow Steven H.
Published: February 2007

The translocation t(15;17) associated with acute promyelocytic leukemia (APL) results in fusion of the retinoic acid receptor alpha (RARA) gene on chromosome 17 with the putative transcription factor gene, PML, on chromosome 15. We report three cases of APL with complex cytogenetic translocations and five cases with atypical phenotypic features with rearrangements within or adjacent to the second intron of the RARA gene. Two patients demonstrated three‐way translocations involving chromosomes 3, 15, and 17, but with differing breakpoints on the short arm of chromosome 3. A third patient developed a complex karyotype at the time of third relapse, but with no change in RARA and PML gene rearrangement pattern. Three patients had normal karyotypes; however, only small numbers of cells could be analyzed. One patient's leukemic cells expressed the T‐cell‐associated antigen CD2 and revealed T‐cell receptor β and γ gene rearrangements. The localization of breakpoints to the second intron of the RARA gene in cytogenetically and phenotypically atypical cases provides additional support for a requisite role of the PML/RARA fusion gene in the pathogenesis of APL. Genes Chrom Cancer 9:49‐56 (1994). © 1994 Wiley‐Liss, Inc.
Localization of amplified MYC gene sequences to double minute chromosomes in acute myelogenous leukemia
Authors: Slovak Marilyn L. , Ho Jennifer Pelkey , Pettenati Mark J. , Khan Aziz , Douer Daniel , Lal Shail , Thomas Traweek S.
Published: February 2007

Cytogenetic and molecular studies were performed on two dmin‐bearing acute myelogenous leukemia (FAB‐M2) samples. Both cases were characterized by complex karyotypes containing interstitial deletions of the long arm of chromosome 8 altering band 8q24.1, aberrations affecting the short arm of chromosome 17, and multiple double minute chromosomes (dmin). Using a 1.4 kb cDNA probe coding for the third exon of the MYC oncogene, DNA slot blots indicated MYC gene sequences were amplified in both samples. Fluorescence in situ hybridization using a 9.0 kb genomic probe for MYC was performed in one we and localized the amplified MYC gene sequences to the dmin. Neither patient achieved a complete remission using traditional induction chemotherapy. The complex karyology with amplification of MYC gene sequences appears to represent a poor prognostic subgroup of acute myelogenous leukemia. Genes Chrom Cancer 9:62‐67 (1994). © 1994 Wiley‐Liss, Inc.
Cardiac myxoma characterized by clonal telomeric association
Authors: Richkind Kathleen E. , Wason Debra , Vidaillet Humberto J.
Published: February 2007

We report on the cytogenetic analysis of a case of cardiac myxoma of the “syndrome myxoma” type, in which clonal telomeric associations between chromosomes 13 and 15, as well as nonclonal telomeric associations between chromosomes 12 and 17 and between chromosome 2 and an unidentified chromosome were observed. Nonclonal structural abnormalities were also present. This is the second reported case of cytogenetic abnormalities of syndrome cardiac myxoma, and the fourth case in which telomeric associations have been described. Genes Chrom Cancer 9:68‐71 (1994). © 1994 Wiley‐Liss, Inc.
Deletion mapping of the short arm of chromosome 3 in human malignant mesothelioma
Authors: Lu You Yong , Cheng Jin Quan , Testa Joseph R. , Jhanwar Suresh C.
Published: February 2007

Previous cytogenetic investigations have revealed frequent deletions and ocher unbalanced structural rearrangements of 3p in human malignant mesothelioma. We have performed a restriction fragment length polymorphism analysis by using the polymerase chain reaction and primer sets for seven DNA markers to examine loss of heterozygosity (LOH) from 3p in 25 malignant mesotheliomas. Among 24 cases informative at one or more 3p loci, 15 (62.5%) exhibited LOH with at least one marker. Deletion mapping in these tumors indicates that the common region of chromosomal loss resides within band 3p21, in the vicinity of the D3F15S2 locus. These results suggest that allelic loss from 3p21 is a frequent Occurrence in malignant mesothelioma and that one or more putative tumor suppressor genes at this site contribute to the pathogenesis of this malignancy.Genes Chrom Cancer 9:76‐80 (1994). © 1994 Wiley‐Liss, Inc.
The spectrum of TP53 mutations in bladder carcinoma
Authors: Williamson Magali P. , Elder Patricia A. , Knowles Margaret A.
Published: February 2007

The mutational spectrum for the TP53 gene was investigated in a large series of bladder tumors and bladder tumor cell lines. Tumors and cell lines were screened for the presence of TP53 point mutations by single‐strand conformational polymorphism analysis followed by direct sequencing. Mutations were detected in 16 of 88 (18%) tumors and 4 of 14 cell lines (28%). In total, twelve missense mutations, one nonsense mutation, three deletions, and two insertions were identified by direct sequencing. Of the thirteen point mutations sequenced, only one was a transition at a CpG site, whereas five G:C → T:A transversions were found, suggesting a major role for exogenous mutagens in bladder tumorigenesis. Tumors were also examined for loss of heterozygosity (LOH) on chromosome arm 17p. LOH of one or more markers on 17p was detected in 31 % of tumors. All eight tumors with a TP53 mutation from patients informative at TP53 had LOH, whereas nine tumors with LOH at TP53 did not have an identified mutation. Three tumors had LOH on 17p at sites distal to the TP53 locus but retained both TP53 alleles, suggesting the involvement of another tumor suppressor gene on 17p in bladder tumorigenesis in some tumors. Genes Chrom Cancer 9:108‐118 (1994).© 1994 Wiley‐Liss, Inc.
Dedifferentiated chondrosarcoma with t(9;22)(q34;q 11‐12)
Authors: Tarkkanen Maija , Knuutila Sakari , Wiklund Tom , Virolainen Martti , Elomaa Inkeri
Published: February 2007

Translocation t(9;22)(q22‐31;q 1 1‐12) is associated with the myxoid variant of chondrosarcorma We present here a report of a patient with a dedifferentiated grade IV chondrosarcorna, which originated from the iliac bone and contained areas of grade I chondrosarcoma There was no evidence of myxoid differentiation. The tumor had the karyotype 46,X,‐X,t(9;22)(q34;q 1 1 ‐12). + mar[5]/52‐61,x?,2‐3dmin,inc[9]/46,XX[2]. It is possible that the different breakpoints in the t(9;22) may reflect different histopathologic subgroups of chondrosarcoma. Genes Chrom Cancer 9:136‐140 (1994). © 1994 Wiley‐Liss, Inc.
Deletion mapping reveals two regions of chromosome 8 allele loss in colorectal carcinomas
Authors: Yaremko M. Lisa , Wasylyshyn Marina L. , Paulus Kristen L. , Michelassi Fabrizio , Westbrook Carol A.
Published: February 2007

Colorectal carcinogenesis is associated with the accumulation of genetic changes involving both dominant oncogenes and tumor suppressor genes. Although at least four different genes have been implicated in the process, the detection of allele loss from other regions of the genome suggests the involvement of additional genes. The short arm of chromosome 8 is one of these regions; loss of heterozygosity occurs at rates ranging from 30 to 50%. To define the region of common deletion containing the putative tumor suppressor gene, we analyzed a series of 87 carcinomas for allele loss in different regions of the short arm of chromosome 8 by using Southern blot analysis and a panel of polymorphic probes. We found allele loss in 33% of our cases, which involves two separate regions, one in the p‐terminal region of the chromosome, 8p23.1 ‐pter, where 45% of informative cases demonstrated loss, and the other in the mid‐p region, at 8p21, where 31% of cases showed allele loss. No tumors showed loss of heterozygosity for both regions. These findings suggest the presence of two discrete genes related to colorectal carcinogenesis on the short arm of chromosome 8. Genes Chrom Cancer 10:1–6 (1994). © 1994 Wiley‐Liss, Inc.
Myelodysplastic syndrome transforming to acute promyelocytic‐like leukemia with trisomy and rearrangement of chromosome II
Authors: Najfeld Vesna , Chen Alex , Scalise Angela , Ambinder Edward P. , Fernandez Gloria , Waxman Samuel
Published: February 2007

Variants of the t(15;17)(q22;q12‐q21) chromosomal rearrangement associated with acute promyelocytic leukemia (APL) have been previously described and they frequently involve either chromosome 15 and/or 17. Previously we reported a rare variant t(11;17). We now describe two patients with myelodysplastic syndrome (MDS) that transformed to APL‐like leukemia. Both had trisomy 11 at the diagnosis of APL‐like leukemia. Following treatment for APL, patient I reverted to MDS and showed a normal karyotype. When leukemia recurred, his bone marrow karyotype was 47,XY,t(4;11), +11,der(22)t(1;22). Both patients were treated with all‐trans retinoic acid (ATRA) for APL for 5 weeks, but failed to respond. The karyotype of patient I after ATRA treatment was 46,XY,t(4;11); the trisomy 11 had been lost and the bone marrow was replaced with immature myeloblasts without promyelocytes. In patient 2, the karyotype remained the same as at diagnosis, i.e., 47,X,‐Y,dir ins(4;7),del(5), +6,del(7), +8, +11,‐18. Molecular analysis by reverse transcriptase PCR analysis showed the presence of wild type retinoic acid receptor alpha (RARA) and the absence of the PML‐RARA chimeric gene associated with t(15;17). Additional analysis of PLZF, a new zinc finger gene associated with t(11;17), also showed the absence of this hybrid gene. These data support the concept that APL is a heterogeneous disorder and that variants with chromosome 11 rearrangement exist that do not respond to ATRA. Genes Chrom Cancer 10:15–25 (1994). © 1994 Wiley‐Liss, Inc.
Deletion of a common region on the long arm of chromosome 6 in acute lymphoblastic leukaemia
Authors: Menasce Lia P. , Orphanos Vassilis , Santibanez‐Koref Mauro , Boyle John M. , Harrison Christine J.
Published: February 2007

We have characterised a region of deletion on the long arm of chromosome 6 (6q) in six cases of acute lymphoblastic leukaemia, by fluorescence in situ hybridisation, using a series of YAC clones which map to 6q. Conventional cytogenetic analysis of four of these cases had been interpreted as showing terminal deletions of 6q. We demonstrated by FISH that in all cases the deletions were interstitial. D6S246 (6q16.3) was the only marker which was missing in all six cases, indicating a common region of deletion between the markers M6PI at 6q14–15 and FYN at 6q21. Our results suggest the presence of a tumour suppressor gene within this interval. Genes Chrom Cancer 10:26–29 (1994). © 1994 Wiley‐Liss, Inc.
Deletions on chromosome 22 in sporadic meningioma
Authors: Ruttledge Martin H. , Xie Ya‐Gang , Han Fei‐Yu , Peyrard Myriam , Collins V. Peter , Nordenskjöld Magnus , Dumanski Jan P.
Published: February 2007

Meningiomas are the second most common group of primary central nervous system tumors in humans. Cytogenetic and molecular studies imply that genes involved in the primary development of meningioma reside on chromosome 22. The recently characterized neurofibromatosis type 2 gene (NF2) has been shown to be mutated in two cases of sporadic meningioma, suggesting that this is the chromosome 22 gene which is involved in tumorigenesis. We have investigated a series of 170 meningiomas by deletion mapping analysis with 43 markers from chromosome 22 to ascertain if NF2 is the only gene on this autosome that is inactivated. Half of the tumors showed results consistent with monosomy for chromosome 22, whereas 13 cases showed terminal deletions of 22q, including the NF2 region. Homozygous (complete) deletions were detected in tumors from two patients. In one of them complete loss was found at the NF2 locus and cosmid contigs from the region were used to determine the extent of the deletions. The second tumor showed homozygous loss of two large genomic regions outside the NF2 region. These aberrations were confined to only one part of this large tumor, suggesting that they may be involved in the later stages of meningioma development An additional four tumors had interstitial deletions on chromosome 22, in three of them without overlap with NF2. Our results show that NF2 is completely inactivated in sporadic meningioma but do not rule out the possibility that additional chromosome 22 loci are important in tumorigenesis. Genes Chromosom Cancer 10:122–130 (1994). © 1994 Wiley‐Liss, Inc.
Identification of a subclass of double minute chromosomes containing centromere‐associated DNA
Authors: Hammond David W. , Hancock Barry W. , Goyns Malcolm H.
Published: February 2007

In a study of abnormal chromosomes in non‐Hodgkin's lymphoma (NHL) cells we have identified one case which contained extrachromosomal chromatin bodies that, on the basis of their morphology and negative C‐banding, appeared to be double minute chromosomes (dmin). However, fluorescence in‐situ hybridization (FISH) analysis using an X‐specific centromeric alphoid repeat probe and a pan‐centromere probe, clearly demonstrated the presence of centromere‐associated DNA in these dmin. FISH analysis with the pan‐centromere probe of the dmin in neuroblastoma and sarcoma cells failed to reveal the presence of centromere‐associated DNA, but analysis of two cases of acute myeloid leukaemia cells revealed centromere‐associated DNA in 25% of their dmin. These data indicate the existence of dmin that contain centromere‐associated DNA and suggest that such dmin might represent a new class of extrachromosomal chromatin bodies. Genes Chromosom Cancer 10:139–142 (1994). © 1994 Wiley‐Liss, Inc.
Clonal karyotypic abnormalities in colorectal adenomas: Clues to the early genetic events in the adenoma‐carcinoma sequence
Authors: Bomme Lilian , Bardi Georgia , Pandis Nikos , Fenger Claus , Kronborg Ole , Heim Sverre
Published: February 2007

Cytogenetic analysis of short‐term cultures from colorectal adenomas revealed acquired clonal chromosome aberrations in 14 of 17 tumors. In 4 adenomas, only numerical changes were found, whereas 10 had structural rearrangements. Trisomy 7 was found as the sole change in one of the tumors and together with other numerical changes in another. A + 7 was also present in one case with structural aberrations. Other recurrent numerical aberrations were −14 and −18, both found in 2 adenomas with structural karyotypic changes; in addition, one chromosome 14 was lost in one of the tumors with only numerical changes. The chromosome most often involved in structural aberrations was chromosome I. In 6 cases, the rearrangements led to changes in l p, always with loss of material. The breakpoints were at l p32–36. One adenoma had deletion of l p as the only change. Other chromosomes that were involved in changes in more than 2 cases were chromosomes 8, 13, and 17. These rearrangements typically led to gain of 8q and 13q and loss of 17p. The adenomas with structural abnormalities were generally larger and had a higher degree of dysplasia than did the adenomas with numerical changes only or those with a normal karyotype. All adenomas with a tubulovillous or villous architecture had structural rearrangements. Our findings confirm that a subset of colorectal adenomas exists that have only numerical chromosome aberrations. They also support our previous conclusion that loss of material from distal l p is an early event in colorectal tumorigenesis, but that other cytogenetic aberrations follow and typically are present already at the adenomatous stage. The accumulation of chromosome‐level mutational events in adenomas correlates with the pathologic features: the more malignancy‐like the phenotype, the more complex the karyotype. There seems to be no single aberration that distinguishes colorectal adenomas from carcinomas, however. Genes Chromosom Cancer 10:190–196 (1994). © 1994 Wiley‐Liss, Inc.
Numerical chromosome changes in a nasal polyp
Authors: Vanni Roberta , Medda Celestino , Marras Susanna , Gaudio Rosa M. , Faa Gavino
Published: February 2007

The etiology of nasal polyposis is not fully understood. We found numerical chromosome changes in one out of five cytogenetically investigated nasal polyps. The histological picture of this case was characterized by the presence of histiocyte‐like cells, which were absent in the remaining cytogenetically normal polyps. Genes Chromosom Cancer 10:203–206 (1994). © 1994 Wiley‐Liss, Inc.
Complex karyotypic abnormalities in a primary carcinoma of the fallopian tube
Authors: Bardi Georgia , Sukhikh Tatjana , Pandis Nikos , Hølund Berit , Heim Sverre
Published: February 2007

Short‐term cultures from a primary carcinoma of the Fallopian tube, a tumor type not characterized before by chromosome banding, were examined cytogenetically. Comlex ahocmosome aberratinss were found in all mitoses, yielding the karyotype 41,XX,del(1)(p34),del(2)(q31),i(8)(q10),‐9, + dic(9;19)(p13;p13), der(12)t(9;12)(p11;q22),‐13,‐16,‐17,‐18,‐19,‐22, +r [61]/84–86,idemx2[15]. Several of the aberrations in the present case are similar to changes found in adenocarcinomas of other organs, including carcinomas of the ovaries and uterus, indicating pathogenetic similarities between Fallopian tube malignancies and the more common gynecologic cancers. Genes Chromosom Cancer 10:207–209 (1994). © 1994 Wiley‐Liss, Inc.
Two distinct deleted regions on the short arm of chromosome I in neuroblastoma
Authors: Schleiermacher Gudrun , Peter Martine , Michon Jean , Hugot Jean‐Pierre , Vielh Philippe , Zucker Jean‐Michel , Magdelénat Henri , Thomas Gilles , Delattre Olivier
Published: February 2007

The short arm of chromosome Ip is the most frequently altered chromosome segment in neuroblastoma. The alterations, mainly deletions, are thought to be indicative of the presence of a tumor suppressor gene. To further refine the chromosome localization of this gene, we have studied paired constitutional and tumor DNA from a series of 60 patients with neuroblastoma at 2 minisatellite and 23 microsatellite loci dispersed along the short arm of chromosome I. Twenty‐two cases (37%) demonstrated loss of heterozygosity (LOH) at one or more loci on 1p. Surprisingly, the pattern of LOH enabled the identification of two distinct consensus regions of deletions. In agreement with previous reports, one region mapped to the distal short arm of chromosome 1. The other region was localized more proximally on 1p. Deletions observed in tumors involve either one or both of these regions. We show that the correlation between NMYC amplification and 1p deletion is limited to the deletions which involve the proximal region either alone or together with the distal region. These results suggest that two tumor suppressor genes on lp might be involved in the development of neuroblastoma. Finally, we show that somatic mutations at microsatellite loci, frequently observed in other types of cancer, are rare events in neuroblastoma. Genes Chromosom Cancer 10:275–281 (1994). © 1994 Wiley‐Liss, Inc.
Common region of deletion on the long arm of chromosome 6 in non‐Hodgkin's lymphoma and acute lymphoblastic leukaemia
Authors: Menasce Lia P. , Orphanos Vassilis , Santibanez‐Koref Mauro , Boyle John M. , Harrison Christine J.
Published: February 2007

We have used fluorescence in situ hybridisation (FISH) with a series of yeast artificial chromosome (YAC) clones that map to the long arm of chromosome 6 (6q) to define the region(s) of deletion in seven cases of non‐Hodgkin's lymphoma (NHL), in which a deletion of 6q had been detected by conventional cytogenetics. The FISH analysis detected two regions of deletion: (i) A proximal region flanked by M6PI (6q 14–15) and FYN (6q21), containing D6S246, which was missing in all seven cases. This locus was also found to be deleted in all six cases of acute lymphoblastic leukaemia (ALL) studied previously, (ii) A second region of 6q, which was distal to 6q23.1 (D6S238) and included ESR (6q25.l) and D6S281 (6q27), which was shown to be present in all our cases of ALL, was found to be deleted in 4 of the 7 cases of NHL. Our results support the suggestion that tumour suppressor genes, involved in the pathogenesis of lymphoid malignancies, may be present within these regions. Genes Chromosom Cancer 10:286–288 (1994). © 1994 Wiley‐Liss, Inc.