bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular basis of IIq23 rearrangements in hematopoietic malignant proliferations
Authors: Bernard Olivier A. , Berger Roland 
Published: February 2007

AbstractChromosomal abnormalities of the 11q23 band occur frequently in various hematopoietic malignant disorders. Because numerous partner chromosomes have been previously described, it is now important to determine the number of genes involved at 11q23 and to clarify the role of the partner genes. Recent efforts in several laboratories have identified a trithorax‐related gene that is involved in most of the 11q23 abnormalities. The aim of this review is to summarize the recent data concerning these 11q23 rearrangements and the understanding of their consequences.
Correlation between the proportion of Philadelphia chromosome‐positive metaphase cells and levels of BCR‐ABL mRNA in chronic myeloid leukaemia
Authors: Lin Feng , Chase Andrew , Bungey Julie , Goldman John M. , Cross Nicholas C. P. 
Published: February 2007

AbstractWe have sought to define the relationship between the proportion of marrow metaphases showing the Philadelphia chromosome (Ph) and levels of BCR‐ABL mRNA assessed by quantitative polymerase chain reaction (PCR) in patients with chronic myeloid leukaemia (CML). From a total of 141 patients, 164 PCR assays were performed on peripheral blood samples taken within 2 weeks of a bone marrow specimen analysed by cytogenetics. BCR‐ABL mRNA was quantified in all 106 PCR‐positive samples by competitive PCR; results ranged from < 10 to 3.4 × 106 transcripts/μg RNA. Twenty‐one chronic‐phase patients had a median of 5.0 × 105 BCR‐ABL transcripts/μg RNA; no difference in levels of the fusion mRNA was found between 15 Ph‐positive and six Ph‐negative, BCR‐ABL‐positive patients. Ph‐positive metaphases were not detected in any individual who was PCR negative (n = 58) and in only a single patient who was PCR positive with < 103 BCR‐ABL transcripts/μg RNA (n = 44). Conversely, of 41 samples from patients in haematological remission who had >103 BCR‐ABL transcripts/μg RNA, 30 had at least one Ph‐positive metaphase. The highest level of BCR‐ABL transcripts at which Ph‐positive metaphases were not detected was 1.5 × 104. For the 46 patients who had at least one Ph‐positive metaphase, a good correlation (Spearman coefficient = 0.83, P <0.0001) was found between the percentage of Ph‐positive metaphases and BCR‐ABL transcript levels. We conclude that quantitative PCR for BCR‐ABL is an effective method for monitoring CML patients after bone marrow transplantation and is less invasive than conventional cytogenetic studies of bone marrow. © 1995 Wiley‐Liss, Inc.
Molecular analysis of a t(II;22) translocation junction in a case of Ewing's sarcoma
Authors: Bhagirath Thounaojam , Abe Syuiti , Nojirna Takayuki , Yoshida Michihiro C. 
Published: February 2007

AbstractPolymerase chain reaction (PCR)‐directed sequence analysis was performed to characterize the genomic and cDNA breakpoint junctions of t(11; 22) (q24; q12) translocation in a case of Ewing's sarcoma, in which the EWS gene located on chromosome 22 is rearranged with the FLII gene located on chromosome 11. RNA‐PCR revealed the novel chimeric product of EWS/FLII gene on the derivative chromosome (der) 22, resulting from a probable fusion of EWS exon 7 to FLII exon 9. Sequencing of the PCR‐amplified genomic fragments of the fusion genes showed that the breakpoints on der(22) occurred in EWS intron 7 and, most probably, in FLII intron 8. Those of the untranxribed counterpart on der(11) were located in the same FLII intron and in EWS exon 11, with deletion of a considerable amount of sequences from both genes. These findings indicate asymmetric junction at the molecular level in the present t(11; 22). None of the reported conserved sequences that mediate other cancer chromosome translocations was observed around the genomic junctions. Instead, a palindromic hexamer 5′‐GCTAGC‐3′ was found to flank the breakpoints of both genes on der(22), which may have a functional significance in the genesis of the t(11; 22). © 1995 Wiley‐Liss, Inc.
BCR/ABL fusion located on chromosome 9 in chronic myeloid leukemia with a masked Ph chromosome
Authors: Mohamed Anwar N. , Koppitch F. , Varterasian M. , Karanes C. , Yao Kai‐Ling , Sarkar F. H. 
Published: February 2007

AbstractA reciprocal translocation, t(10; 22) (q22; q11), resulting in a masked Ph chromosome was identified in a patient diagnosed with chronic myeloid leukemia (CML). Both homologs of chromosome 9 were of the normal pattern. Two signals for the ABL probe, both of them hybridized to chromosome 9, were demonstrated via fluorescence in situ hybridization (FISH). Furthermore, cohybridization with two differently labeled BCR/ABL translocation DNA probes indicated a BCR/ABL fusion apparently located on 9q34. Molecular studies revealed a rearrangement of the BCR region and expression of a chimeric BCR/ABL mRNA of CML configuration. These findings indicate that the BCR/ABL fusion resulted from an unusual relocation of the BCR gene from its normal position on 22ql I to 9q34 adjacent to the ABL gene.
The t(II; 22)(pI5.5; qII.23) in a retroperitoneal rhabdoid tumor also includes a regional deletion distal to CRYBB2 on 22q
Authors: Besnard‐Guérin Corinne , Cavenee Webster , Newshams Irene 
Published: February 2007

AbstractTranslocations and deletions involving chromosomal band 22q 11 are common genetic aberrations in malignant rhabdoid tumors. Previous molecular analyses of a t(11; 22) in the malignant rhabdoid tumor cell line TM87‐16 localized the breakpoint distal to BCR on 22q 11. In the present report, we have further refined the map position of this breakpoint between CRYBB2 and D22S258. Moreover, the D22S258, CRYBA4, D22S300, D22SI, and D22S310 loci, which lie between CRYBB2 and D22S42, were found to be deleted, presumably as a result of the translocation event. The identification of this deletion of at least 2 Mb on the long arm of chromosome 22 should be helpful for mapping the gene(s) in the region involved in the development of malignant rhabdoid tumors as well as providing insights into the mechanisms of chromosomal translocation in human solid tumors.
Localization of a tumor suppressor gene associated with progression of human prostate cancer within a 1.2 Mb region of 8p22‐p21.3
Authors: Suzuki Hiroyoshi , Emi Miburu , Komiya Akira , Fujiwara Yoshiyuki , Yatani Ryuichi , Nakamura Yusuke , Shimazaki Jun 
Published: February 2007

AbstractHuman prostate cancers frequently show loss of heterozygosity at loci on the short arm of chromosome 8. In order to take a step toward isolation of the putative tumor suppressor gene(s) on 8p via positional cloning, we performed high‐resolution deletion mapping in 46 prostate cancers (stage B, 20 cases; stage C, 8 cases; endocrine therapy‐resistant cancer death, 18 cases) using new 12 restriction fragment length polymorphism markers for this chromosomal region. Allelic losses were observed in 25 of the 44 cases (57%) that were informative with at least one locus. Detailed deletion mapping defined a 1.2 Mb commonly deleted region at 8p22‐p2 1.3 flanked by markers cMSR‐32 and C18‐ 105 1. A second region of common deletion was identified between C18‐1312 and C18‐494 at 8p21‐8p11.22, suggesting that at least two tumor suppressor genes associated with prostate cancer are present on chromosome arm 8p. Allelic losses on 8p were observed more frequently in the cancer death cases (14/17, 82%) than in early‐stage tumors (11/27, 40%; P < 0.01, Fisher's exact test). In two out of 7 patients for whom DNA was available from metastatic cancers as well as from normal tissues and primary tumors, the primary cancer foci had no detectable abnormality of 8p, but the metastatic tumors showed loss of heterozygosity. These results suggest that inactivation of tumor suppressor genes on 8p plays an important role in the progression of prostate cancer. © 1995 Wiley‐Liss, Inc.
Identification of novel regions of altered DNA copy number in small cell lung tumors
Authors: Levin Nikki A. , Bnorka Piur M. , Warnock Martha L. , Gray Joe W. , Christman Michael F. 
Published: February 2007

AbstractIdentification of the genetic alterations that occur in tumors is an important approach to understanding tumorigenesis. We have used comparative genomic hybridization (CGH), a novel molecular cytogenetic method, to identify the gross DNA copy number changes that commonly occur in small cell lung cancer (SCLC). We analyzed ten SCLC tumors (seven primary tumors and three metastases) from eight patients. We found frequent increases in DNA copy number on chromosome arms Sp, 8q, 3q, and Xq and frequent decreases in copy number on chromosome arms 3p. 17p, Sq, 8p, 13q, and 4p. The increase in copy number at 8q24 (MYC) and decreases at 17p 13 (TP53), 13q 14 (RB), and 3p have previously been identified in SCLC with other methods. Many of the other regions in which we detected common copy number changes have not been reported to be regions of common alteration in SCLC tumors. Comparison of copy number changes between a primary tumor and a metastasis from the same patient showed that they were more closely related to each other than to any of the other tumors. The results of direct CGH analysis of SCLC tumors reported here confirm the existence of copy number changes that we identified previously by using cell lines. © 1995 Wiley‐Liss, Inc.
High allele loss rates at I7q I2‐q2I in breast and ovarian tumors from BRCAI‐linked families
Authors: Cornelis R. S. , Neuhausen S. L. , Johansson O. , Arason A. , Kelsell D. , Ponder B. A. J. , Tonin P. , Hamann U. , Lindblom A. , Lalle P. , Longy M. , Olàh E. , Scherneck S. , Bignon Y. ‐J. , Sobol H. , Chang‐Claude J. , Larsson C. , Spurr N. , Borg A. , Barkardottir R. B. , Narod S. , Devilee P. 
Published: February 2007

AbstractLoss of heterozygosity (LOH) was evaluated in 174 breast and ovarian tumors derived from 94 families with at least 3 first‐degree relatives affected with either of these cancers. By linkage analysis 26 families were identified as having a high posterior probability of being due to BRCAI (the breadovarian cancer susceptibility locus on 17q 12–21) with lod scores varying from 0.5 1 to 9.49. Tumor genotypes were determined at at least 2 constitutionally heterozygous markers flanking BRCA I in a total of 58 tumors from these families. These tumors were derived from 52 patients, the BRCAI mutation carrier status of which was evidenced by DNA sequencing in 20, and inferred by reconstructing haplotypes in the remainder. LOH was detected in 50 (86%) tumors. and invariably involved the wild‐type allele. Where informative, this allele was of paternal origin in 33 cases and of maternal origin in I0 cases. These results strongly suggest that BRCA I is a tumor suppressor gene and that LOH is greatly favored to fully inactivate it. © 1995 Wiley‐Liss, Inc.
Predominant occurrence of somatic mutations of the NF2 gene in meningiomas and schwannomas
Authors: Mérel P. , Hoang‐Xuan K. , Sanson M. , Moreau‐Aubry A. , Bijlsma E. K. , Lazaro C. , Moisan J. P. , Resche F. , Nishisho I. , Estivill X. , Delattre J. Y. , Poisson M. , Theillet C. , Hulsebos T. , Delattre O. , Thomas G. 
Published: February 2007

AbstractThe NF2 gene is a putative tumor‐suppressor gene that, when it is altered in the germline, causes neurofibromatosis type 2, a tumor‐susceptibility disease that mainly predisposes to schwannomas and meningiomas. The recent isolation of the NF2 gene on chromosome 22 allows the identification of somatic mutations in human tumors. We have searched for mutations of the NF2 gene in 331 primary human tumors using a screening method based on denaturing gradient gel electrophoresis, which allows the detection of mutations in 95% of the coding sequence. Mutations were observed in 17 of 57 meningiomas and in 30 of 89 schwannomas. No mutations were observed for 17 ependymomas, 70 gliomas, 23 primary melanomas, 24 pheochromocytomas, 15 neuroblastomas, 6 medulloblastomas, 15 colon cancers, and 15 breast cancers. All meningiomas and one‐half of the schwannomas with identified NF2 mutations demonstrated chromosome 22 allelic losses. We conclude that the involvement of the NF2 gene in human tumorigenesis may be restricted to schwannomas and meningiomas, where it is frequently inactivated by a two‐hit process. © 1995 Wiley‐Liss, Inc.
U937 cell line has a t(I0;II)(pI3–I4;qI4–2I) rather than a deletion of IIq
Authors: Kobayashi Hirofumi , Thirman Michael J. , Rowley Janet D. 
Published: February 2007

AbstractThe U937 cell line was studied with the fluorescence in situ hybridization (FISH) technique using phage and cosmid probes which were mapped and ordered on IIq. Although this cell line was thought to have a del(IIq), FISH demonstrated that IIq was translocated to lop and that the breakpoint on IIq is centromeric to the MLL gene. This I0; II translocation appears to be a t(I0;II)(p I3‐I4;q I4–2I), which was recently reported to be a recurring translocation in malignant hematologic disease. This cell line will be a good tool for the study of this chromosomal rearrangement.
BCL6 encodes a sequence‐specific DNA‐binding Protein
Authors: Baron Beverly W. , Stanger Regan R , Hume Ellen , Sadhu Annamma , Mick Rosemarie , Kerckaert Jean‐Pierre , Deweindt Clotilde , Bastard Christian , Nucifora Giuseppina , Zeleznik‐Le Nancy , McKeithan Timothy W. 
Published: February 2007

AbstractChromosomal rearrangements of BCL6 are commonly associated with diffuse large‐cell lymphomas. We set out to determine the DNA‐binding site of a glutathione‐S‐tranderase fusion protein containing the BCL6 zinc finger region by employing cyclic amplification and selection of targets (CASTing). From oligonucleotides containing 16 central random bases, sequences binding to the protein on glutathione‐coated beads were repeatedly selected and amplified by polymerase chain reaction (PCR). The binding sites were cloned and sequenced. A consensus, TTTNNNGNNATNCTTT, was obtained. Protein binding studies of double‐stranded oligomen containing point mutations within the 3′ CTTT confirmed the binding specificity of this part of the consensus. In addition, evidence indicated that some of the base pairs held constant in the oligonucleotides used for CASTing also contributed to binding. © 1995 Wiley‐Liss, Inc.
Loss of heterozygosity on chromosome arms 5q, IIp, IIq, I3q, and I6p in Human Testicular Germ Cell Tumors
Authors: Al‐Jehani Rajai M. A. , Povey Susan , Delhanty Joy D. A. , Parrington Jennifer M. 
Published: February 2007

AbstractTo identify common regions of deletion in human testicular germ cell tumors (TGCTs), we have screened tumors from 33 patients for loss of heterozygosity (LOH) using Southern blot analysis with 39 polymorphic markers covering 21 chromosome arms. Losses in more than 2 tumors and occurring at a frequency of > 10% were found on chromosome arms 5q, 11p, 11q, 13q, and 16p, the highest being on chromosome arm 5q (19%). It is suggested that tumor suppressor genes on 5q among others may be involved in testicular tumorigenesis and that LOH in this region requires further investigation. No losses were found on 12q and 17p despite the fact that the most common cytogenetic abnormality in TGCTs is an i( 12p) and that the TP53 gene on 17p is the most frequently mutated gene in human cancers. The level of allelic imbalance varied considerably from one chromosome region to another (0–80%) and did not generally reflect the pattern of LOH. It tended to be high in overrepresented regions of the genome, 1q, 7p, and 12p. The tumor from one patient had a seminomatous component and a less differentiated component. We provide evidence for a common origin of both components and show that it is likely that this tumor has progressed from the seminoma to the less differentiated histology. © 1995 Wiley‐Liss, Inc.
In situ hybridization analysis of the Y chromosome in gonadoblastoma
Authors: Sultana Razia , Myerson David , Disteche Christine M. 
Published: February 2007

AbstractGonadoblastoma is a rare tumor arising in the streak gonads of about 30% of 46, XY sex‐reversed females. Because gonadoblastoma develops only in patients who have Y‐chromosome material and dysgenetic gonads, it has been hypothesized that positive expression of a gene (or genes) on the Y chromosome (GBY) is involved in the etiology of the tumor. To examine the Y chromosome directly in tumors, we performed nonisotopic in situ hybridization of a biotin‐labeled Y‐specific probe for the DYZI locus on formalin‐fixed, paraffin‐embedded sections of tumor samples from four different patients.After hybridization to DYZI, the Y chromosome was found to be present in all gonadoblastoma foci in the four patients studied, and the gonadoblastoma foci showed an average of 85% cell nuclei positive for the Y chromosome on tissue sections. Normal male and female control tissues showed an average of 78% and 0% positive nuclei, respectively. One patient with bilateral gonadoblastoma had previously been shown to be mosaic, with a 45, X/46, XY karyotype in lymphocytes, skin fibroblasts, and cultures from both gonads. Examination of sections of this patient's gonads showed 79% positive nuclei within the gonadoblastoma foci, whereas the nontumor stromal tissue had 19% positive nuclei. These results indicate that, in this mosaic gonad, tumor foci developed only from cells that had a Y chromosome. Our results support the hypothesis that there is a GBY locus on the Y chromosome and that the Y chromosome is retained in the gonadoblastoma foci during the development of the tumor. © 1995 Wiley‐Liss, Inc.
Genomic DNA and messenger rna expression alterations of the CDKN2B and CDKN2 genes in esophageal squamous carcinoma cell lines
Authors: Zhou Xiaoling , Suzuki Hiroyuki , Shimada Yutaka , Imamura Masayuki , Yin Jing , Jiang Hai‐Yan , Tarmin Lila , Abraham John M. , Meltzer Stephen J. 
Published: February 2007

AbstractThe genes CDKN2B (MTS2) and CDKN2 (MTSI) encoding the proteins p15 and p16 are both located on chromosomal band 9p21, a locus at which frequent homozygous and heterozygous deletions occur in many primary human tumors, including esophageal carcinoma. CDKN2 and CDKN2B belong to a family of cyclin‐dependent kinase 4 inhibitors (INK41) and control cell proliferation during the GI phase of the cell cycle. Their inactivation may contribute to uncontrolled growth in human cancers. To investigate whether CDKN2B and CDKN2 are involved in esophageal tumorigenesis, we studied homozygous deletion, intragenic mutation, and messenger RNA (mRNA) expression of CDKN2 and CDKN2B in nine esophageal squamous cancer cell lines. Polymerase chain reaction (PCR) amplification revealed that five of the nine cell lines (55%) manifested homozygous deletions of CDKN2B, CDKN2, and/or flanking loci on chromosomal band 9p21. Reverse transcriptase‐PCR (RT‐PCR) was used to examine CDKN2 and CDKN2B mRNA in the nine cell lines. Lack of CDKN2 and CDKN2B mRNA correlated perfectly with homozygous deletion involving these genes. No subtle intragenic mutations of CDKN2B or CDKN2were detected by DNA sequencing of their entire coding sequences in any cell lines lacking homozygous deletion. Two of the cell lines manifested homozygous deletions excluding CDKN2; one of these two deletions also excluded CDKN2B. These results suggest that inactivation of CDKN2B and CDKN2 may contribute to the malignant phenotype in esophageal cells and that homozygous deletion may be the predominant mechanism for inactivation of CDKN2B and CDKN2. Alternatively, a gene or genes adjacent to CDKN2B/CDKN2 may constitute the target(s) of deletion at this locus. © 1995 Wiley‐Liss, Inc.
Patterns of loss of heterozygosity at loci from chromosome arm 13q suggest a possible involvement of BRCA2 in sporadic breast tumors
Authors: Kerangueven Fabienne , Allione Florence , Noguchi Teburo , Adélaïde José , Sobol Hagay , Jacquemier Jocelyne , Birnbaum Daniel 
Published: February 2007

AbstractLoss of heterozygosity (LOH) at loci from chromosome I3 is frequently observed in breast cancer. Chromosome 13 contains at least two cancer genes, the well‐characterized RB1 gene located at 13q 14 and the breast cancer‐susceptibility gene, BRCA2, recently localized to 13q 12. To investigate the possible involvement of BRCA2 in sporadic breast tumors, we looked at LOH at eight microsatellite (CA)n markers distributed along chromosome 13 in a panel of 59 primary breast carcinomas. We show that some LOH does not include the RB1 locus and is associated with the BRCA2 gene region.
Fluorescence in situ hybridization identifies new chromosomal changes involving 3q27 in non‐Hodgkin's lymphomas with BCL6/LAZ3 rearrangement
Authors: Wlodarska Iwona , Mecucci Cristina , Stul Michel , Michaux Lucienne , Pittaluga Stefania , Hernandez Jesus Maria , Cassiman Jean‐Jacques , De Wolf‐Peeters Christiane , van den Berghe Herman 
Published: February 2007

AbstractTwelve B‐cell non‐Hodgkin's lymphomas with BCL6/LAZ3 rearrangement selected from a series of 30 lymphomas with cyto‐genetically detectable 3qter abnormalities were characterized at the histological, clinical, and cytogenetic levels, including fluorescence in situ hybridization (FISH) analysis, which was performed in all cases but one. A classical t(3;14) and t(3;22) were found in three patients (25%). In the remaining cases, eleven different 3q27 abnormalities were demonstrated and characterized with the use of chromosome painting. Seven of twelve “variant” rearrangements identified in our series affecting 1p32, 1p34, 3p14, 6q23, 12p13, 14q11, and 16p13 have not been reported before. Moreover, involvement of both homologs of chromosome 3 in distinct translocations was detected as an unexpected result in two cases and was confirmed via FISH in a third case. The putative bichromosomal rearrangements of the 3q27 region were evidenced by Southern analysis in one of these cases. In another case, FISH with a cosmid spanning the 3q27 breakpoint region demonstrated the involvement of BCL6/LAZ3 only in one of two t(3q27).In our series, which was selected on cytogenetic and molecular criteria, 50% (6 of 12) of cases with BCL6/LAZ3 rearrangement were diagnosed as diffuse, large B‐cell lymphomas (DLCL). Another 33% (4 of 12) of cases were diagnosed as follicular center lymphomas (FL), with t(14;18)/BCL2 rearrangement in all but one case. Furthermore, in three follicular lymphoma cases in which multiple samples were analyzed, the disease showed no evidence of histological progression during a follow‐up period of 3‐14 years. The present data show that rearrangement of BCL6 is not restricted to high‐grade malignancies as was previously suggested but can also occur in low‐grade lymphomas. In addition, the appearance of BCL6/LAZ3 rearrangement in follicular lymphomas is not related to disease progression.
κ‐ and λ‐positive cells in centroblastic‐centrocytic lymphoma (follicular lymphoma) may share a secondary chromosome aberration: Reflections on early lymphoma development
Authors: Weber‐Matthiesen Klaus , Winkemann Martin , Grote Werner , Schlegelberger Brigitte 
Published: February 2007

AbstractThe technique of simultaneous fluorescence immunophenotyping and interphase cytogenetics (FICTION) was applied in four cases of centroblastic‐centrocytic (working formulation: follicular) lymphoma. Our aim in this study was to establish whether secondary chromosome aberrations known from a prior cytogenetic analysis were detectable in both κ‐ and λ‐expressing tumor cells from the same lymphoma patient. One of the cases did indeed contain κ‐ and λ‐positive tumor cells with trisomy 8. On the basis of our results, we reflect on the events that take place during early development of centroblastic‐centrocytic lymphoma.