bluuebunny/crossref_metadata_2025_split huggingface dataset:
RAS gene mutations in childhood acute myeloid leukemia: A pediatric oncology group study
Authors: Vogelstein Bert , Civin Curt I. , Preisinger Antonette C. , Krischer Jeffrey P. , Steuber Philip , Ravindranath Y. , Weinstein Howard , Ellferich Peter , Bos Johannes 
Published: February 2007

AbstractMutations at codon 12, 13, and 61 of the HRAS, KRAS, and NRAS genes were evaluated in 99 cases of pediatric acute myeloid leukemia (AML) using oligonucleotide hybridization to polymerase chain reacted derived products. Twenty‐four mutations were identified in the NRAS gene, 13 in the KRAS gene, and none in the HRAS gene. The mutations occurred in a broad spectrum of cases, and there was no specific association of RAS gene mutations with patient subsets defined on the basis of clinical or hematologic features. These data demonstrate that RAS gene mutations are at least as common in childhood AML as in adult AML and suggest that RAS gene mutations play a role in myeloid neoplasia in both age groups.
The 11q13 amplicon of a mammary carcinoma cell line
Authors: Lafage Marina , Nguyen Catherine , Szepetowski Pierre , Pébusque Marie‐Josèphe , Simonetti Jacqueline , Courtois Geneviéve , Gaudray Patrick , Delapeyriere Odile , Jordan Bertrand , Birnbaum Daniel 
Published: February 2007

AbstractFifteen to 20% of breast carcinomas show amplification of genes located at 11q13. The HST/FGFK and INT2 fibroblast growth factor (FGF)‐related genes and the BCL1 locus are usually present in the amplification units. We have investigated the structure and chromosomal location of the 11q13 amplicon of the MDA‐MB‐134 mammary carcinoma cell line by using in situ chromosomal and pulsed field gel hybridizations. The results indicate that a limited number of amplification units are involved in the constitution of an extended chromosomal region located on 11q. These units do not show any important rearrangement over rather large distances around the HST/INT2 and BCL1 loci.
Genomic alterations in human breast carcinomas
Authors: Larsson Catharina , Byström Camilla , Skoog Lambert , Rotstein Sam , Nordenskjöld Magnus 
Published: February 2007

AbstractAll human chromosomes were screened in 52 human breast carcinomas for the occurrence of allele losses, in order to identify genomic alterations involved in initiation and progression of the disease. Loss of chromosome 22 alleles was detected in 6 out of 8 lobular carcinomas, while chromosome 17 losses were most frequent in ductal carcinomas. Furthermore, patients who developed advanced disease after many years of mild clinical course showed significantly higher frequencies of allele losses in their primary tumors, compared to patients with a persistently mild disease course. Finally, in one case, molecular examination suggested a translocation t(10;17) with coamplification of the ERBB2 oncogene and chromosome 10 sequences present in the two tumors from this patient, consistent with one of the tumors being a metastasis originating from a subclone of cells in the other tumor.
Frequent rearrangement of chromosomal bands 1p22 and 11q13 in squamous cell carcinomas of the head and neck
Authors: Jin Yuesheng , Higashi Koichiro , Mandahl Nils , Heim Sverre , Wennerberg Johan , Biörklund Anders , Dictor Michael , Mitelman Felix 
Published: February 2007

AbstractWe report the finding of clonal structural chromosome abnormalities in short‐term cultures from 15 squamous cell carcinomas of the head and neck region. When the distribution of chromosomal breakpoints in these 15 tumors and in the 16 head and neck carcinomas previously described are assessed, a marked clustering is seen at bands 1p22 and 11q13, which are rearranged in eight and nine tumors, respectively. No other band was involved in aberrations in more than five tumors. Cytogenetic evidence of gene amplification was seen in four tumors, three times in the form of homogeneously staining regions (twice located in 11q13), and in one tumor as double minutes. Among the candidate genes for such amplification are BCL1, INT2, and HST1, all of which map to 11q13, and NRAS, which maps to 1p22. All these oncogenes have previously been shown to be amplified in subsets of head and neck carcinomas. We conclude that bands 1p22 and 11q13 are nonrandomly involved in chromosomal rearrangements in head and neck carcinomas and suggest that activation of oncogenes located in these bands may proceed via cytogenetic mechanisms.
Molecular characterization of the t(10;14) translocation breakpoints in T‐cell acute lymphoblastic leukemia: Further evidence for illegitimate physiological recombination
Authors: Lu Ming , Dubé Ian , Raimondi Susana , Carroll Andrew , Zhao Ying , Minden Mark , Sutherland Peter 
Published: February 2007

AbstractThe t(10;14)(q24;q11) translocation is a non‐random chromosome change seen in the leukemic cells of 5–10% of patients with T‐cell acute lymphoblastic leukemia (T‐ALL). Recent studies support the hypothesis that the translocation occurs in the course of aberrant physiological recombination and results in the juxtaposition of a T‐cell receptor (TCR) gene in 14q11 with a putative oncogene, TCL3, in 10q24. We cloned and sequenced the translocation breakpoints on both derivative 10q+ and 14q– chromosomes from a patient with t(10;14)(q24;q11) T‐ALL. Two distinct diversity segments of TCRD, Dδ2 and Dδ3, were identified at the two translocation breakpoints on chromosome 14. The 9.5 kb DNA that separates these two subunits in the germline was deleted, possibly in the course of a D‐D joining event. The two chromosome 10 breakpoints were 10 nucleotides apart and occurred in the immediate vicinity of a pseudo‐heptamer signal motif. N‐region addition is also evident at the breakpoint on the derivative chromosome 10. Our observations strongly suggest that the IG/TCR recombinase normally involved in V‐(D)‐J joining was involved in the process of the t(10;14)(q24;q11) translocation.
Break in the BCL1 locus is closely associated with intermediate lymphocytic lymphoma subtype
Authors: Rimokh Ruth , Berger Françoise , Cornillet Pascale , Wahbi Kamal , Rouault Jean‐Pierre , Ffrench Martine , Bryon Paul‐André , Gadoux Myfène , Gentilhomme Odile , Germain Daniel , Magaud Jean‐Pierre 
Published: February 2007

AbstractThe t(11;14)(q13;q32) is a recurring translocation associated with some chronic B‐cell lymphocytic malignancies; the putative protooncogene BCL1, located at the chromosome band 11q13, can be involved during the translocation process. In order to determine if BCL1 rearrangement is associated with a particular subtype of lymphoma, we analysed 131 B‐cell non‐Hodgkin's lymphoma samples by Southern blot analysis, using a BCL1 probe. The BCL1 locus was rearranged in 9 out of 25 (36%) cases of intermediate lymphocytic cell lymphomas (ILL), in 1 out of 8 cases of diffuse small cleaved cell lymphoma, in 1 out of 12 cases of diffuse mixed cell lymphoma, and in 1 out of 21 cases of diffuse large cell lymphoma. In contrast, BCL1 was never found rearranged in any of the 46 follicular lymphomas analysed. The BCL2 gene was in germ‐line configuration in all ILL. Sequential hybridization of Southern blots with JH, Cμ, and BCL1 probes identified comigrating fragments in only one case of ILL, which suggests that, in all the other cases, either the rearrangement of BCL1 did not result from a t(11;14) translocation or the break on chromosome 14 occurred outside the JH or Cμ regions. These results indicate that rearrangement of the BCL1 locus may be closely associated with ILL and could be considered as a genotypic marker of this lymphoma subtype.
Constitutional translocation t(1;17)(p36;q12–21) in a patient with neuroblastoma
Authors: Laureys Geneviève , Speleman Frank , Opdenakker Ghislain , Benoit Yves , Leroy Jules 
Published: February 2007

AbstractA constitutional chromosome translocation t(1;17)(p36;q12–21) is reported in a boy with neuroblastoma. This is the first description of a cytogenetic abnormality possibly predisposing to the development of neuroblastoma.
Chromosomal breakpoints in cholangiocarcinoma cell lines
Authors: Storto Patrick D. , Saidman Susan L. , Demetris Anthony J. , Letessier Eric , Whiteside Theresa L. , Gollin Susanne M. 
Published: February 2007

AbstractLittle is known about the genetics and biology of cholangiocarcinoma (intrahepatic bile duct carcinoma). Only three human bile duct carcinoma cell lines have been described in the literature. We present the first detailed cytogenetic analysis of two cell lines; a new cell line designated PCI:SG231, established in our laboratory, and RPMI‐7451, a previously established cell line. Both lines had highly aneuploid karyotypes with complex rearrangements including marker chromosomes. PCI:SG231, harvested after 50 days in culture, had a modal and median chromosome number of 65, and many cells contained double‐minute chromosomes. RPMI‐7451 had a modal and median chromosome number of 67. C‐banding confirmed the presence of dicentric chromosomes in PCI:SG231. Q‐banding confirmed the absence of the Y chromosome in PCI:SG231 and the presence of a der(1)t(Y;1)(q11;p11) chromosome in RPMI‐7451. Numerical abnormalities common to both lines included trisomies 2, 5, 11, and 20. Chromosomes 1, 5, 7, and 12 were most commonly involved in structural abnormalities in both lines. Consistent chromosomal breakpoints included 7q22 and 12p11–12 PCI:SG231 was tumorigenic in immunosuppressed nude mice and was histologically similar to the original tumor. Additional cholangiocarcinoma cell lines are being developed to continue the study of the genetics and cell biology of this disorder.
Irradiation microcell‐mediated chromosome transfer (XMMCT): The generation of specific chromosomal arm deletions
Authors: Dowdy Steven F. , Scanlon David J. , Fasching Clare L. , Casey Graham , Stanbridge Eric J. 
Published: February 2007

AbstractThe microcell‐mediated chromosome transfer technique has been used to introduce whole chromosomes into malignant cells and revert the tumorigenic phenotype. However, in most instances the limited availability of selectable chromosomes has hindered the ability to reduce the region containing the tumor suppressive information. The work presented here describes a new method to enrich for specific chromosomal arm deletions of selectable chromosomes and thereby more finely focus upon the genetic region of interest. The irradiation‐microcell mediated chromosome transfer (XMMCT) technique involves the irradiation of microcells containing single human chromosomes followed by fusion to a nonirradiated host and cytogenetic characterization. The XMMCT procedure was performed on a microcell hybrid containing a der(11) as the only human chromosome. The resultant irradiated microcell hybrids were found to have deletions that ranged from simple interstitial deletions to complex deletions/rearrangements involving only the human der(11) chromosome. The XMMCT procedure has broad applications in generating chromosomal reagents for mapping genetic loci and for use in functional analyses such as tumor suppression studies.
Breast cancer and other cancers in Norwegian families with ataxia‐telangiectasia
Authors: Børresen Anne‐Lise , Andersen Tone Ikdahl , Tretli Steinar , Heiberg Arvid , Møller Pål 
Published: February 2007

AbstractPatients who are homozygous for ataxia‐telangiectasia (AT) have an exceptionally high incidence of cancer. Heterozygous individuals for the disease have been reported to be at an increased risk of cancer, particularly breast cancer in female carriers. We have analyzed eight Norwegian families with AT for cancer incidence in the parents, in the parents' sibs, grandparents, and grandparents' sibs. Two of the obligate heterozygote females have had premenopausal breast cancer. This incidence is significantly higher than expected for that group. No increase in the cancer incidence was observed in the parents' sibs, the grandparents, or the grandparents' sibs. Since the incidence of AT is low, data from many sources have to be combined to allow any conclusion.
Consistent cytogenetic aberrations in hepatoblastoma: A common pathway of genetic alterations in embryonal liver and skeletal muscle malignancies?
Authors: Fletcher Jonathan A. , Kozakewich Harry P. , Pavelka Karen , Grier Holcombe E. , Shamberger Robert C. , Korf Bruce , Morton Cynthia C. 
Published: February 2007

AbstractCytogenetic analyses of four consecutive hepatobiastomas revealed near‐diploid stemline karyotypes with relatively simple chromosome aberrations. Cytogenetic abnormalities shared by each tumor included trisomy for all of part of chromosome 2 and trisomy for chromosome 20. In two cases, partial trisomy for chromosome 2 resulted from direct duplication of long arm material with the shortest region of overlap being 2q23‐2q35. In one tumor, each metaphase also contained a variable number of double minute chromosomes found not to derive from NMYC amplification. Interestingly, trisomy for 2q and trisomy 20 are also characteristic events in pediatric embryonal rhabdomyosarcomas. Furthermore, others have reported loss of heterozygosity for the short arm of chromosome 11 in both hepatoblastoma and childhood embryonal rhabdomyosarcoma, and both these malignant diseases are associated with Beckwith‐Wiedemann syndrome. These cytogenetic and molecular findings suggest a parallel pathway of genetic steps in the initiation and/or progression of tumors of embryonal liver and skeletal muscle.
Direct pulsed field gel electrophoresis of Wilms' tumors shows that dna deletions in 11 p 13 are rare
Authors: Royer‐Pokora Brigitte , Ragg Susanne , Heckl‐Östreicher Brigitte , Held Manuela , Loos Ursula , Call Katherine , Glaser Tom , Housman David , Saunders Grady , Zabel Bernhard , Williams Bryan , Poustka Annemarie 
Published: February 2007

AbstractIn order to search for small tumor‐specific deletions in 11 p 13 we analysed DNA isolated from 30 fresh Wilms' tumor (WT) samples with pulsed field gel electrophoresis. For these studies we have isolated new probes from the ends of several Nod fragments. Using these and previously described probes from 11 p 13 we first completed and extended the existing map of the 11 p 13 region. The analysis of the tumor material showed that (1) tumor‐specific deletions were very rare: one homozygous deletion out of 30 tumors analysed, (2) hemizygous deletions were not observed in any of the tumors. The homozygous deletion in one patient spans 220 kb and is composed of a tumor‐specific translocation associated with a deletion on one chromosome and a deletion of about 220 kb on the other chromosome at the same site. The WT‐33 Wilms' tumor candidate gene maps to this deleted segment. A small constitutional deletion of 1,300 kb was identified in a patient with WT and genital tract malformations. These results suggest that in the majority of sporadic WT loss of gene function is due to subtle alterations in the gene, e.g., point mutations or very small deletions.
Expression of the ERBB2 protein in benign and malignant salivary gland tumors
Authors: Stenman Goran , Sandros Jens , Nordkvist Anders , Mark Joachim , Sahlin Pelle 
Published: February 2007

AbstractFifty‐two primary human salivary gland tumors were analyzed for expression of the p 185ERBB2 protein using immunohistochemical and immunoblotting techniques. About 63% (33/52) of the tumors expressed the ERBB2 protein. The highest expression levels were detected among the carcinomas, where 32% of the tumors showed intense membrane staining in 25–100% of the tumor cells. In benign pleomorphic adenomas, the corresponding figure was only 12%. Clinical follow‐up data available for 18 of the 19 patients with carcinomas suggested an association between high ERBB2 protein levels and poor prognosis as measured by recurrence of disease and/or the appearance of metastases. These results indicate that ERBB2 activation and overexpression could be an important genetic event with possible prognostic implications in a subset of malignant salivary gland tumors.
Clonal cytogenetic abnormalities in Hodgkin's disease
Authors: Ladanyi Marc , Parsa Nasser Z. , Offit Kenneth , Wachtel Mitchell S. , Filippa Daniel A. , Jhanwar Suresh C. 
Published: February 2007

AbstractCytogenetic studies of Hodgkin's disease (HD), in contrast to those of non‐Hodgkin's lymphoma (NHL), have been limited to small numbers of cases with infrequently recurring aberrations, underscoring the need for additional studies in establishing a coherent Cytogenetic picture of HD. Over a 6 1/2‐year period, we received 95 specimens of HD for Cytogenetic analysis. Analyzable chromosome preparations were obtained in 70 cases, of which 57 (81 %) showed only normal metaphases. In the remaining 13 cases (19%), karyotypic abnormalities were observed that were nonclonal in 3 and clonal in 10. The latter 10 cases included 6 of the nodular sclerosis subtype, 3 mixed cellularity, and 1 lymphocyte‐depleted; 8 of the specimens were obtained pretreatment and 2 posttreatment. Two of the cases had a clonal numerical aberration, monosomy 17 in one and trisomy 13 in the other, as their sole abnormality. The remaining 8 cases showed complex karyotypes with multiple structural rearrangements; in 3 of these, the abnormal clone was near‐tetraploid. Bands involved more than once included 1p36, 1q21, and 4q35, each in 2 cases. Arms involved more than once included 6q (6q13,6q23), 9p (9p13,9p21), and 5q (5q15,5q35). Three patients had loss of part or all of 6q (del(6)(q 13), del(6)(q23), i(6p)). Bands 14q32 and 18q21 were not involved in any case, contrary to some previous reports. Our results confirm the frequent occurrence of 1 p, 1 q, and 6q abnormalities in HD. In addition, we have identified a 5q35 breakpoint, which has recently been shown to be highly specific for Ki‐1 ‐positive NHL in a case of typical nodular sclerosis HD. Its presence in HD may represent a Cytogenetic link between the two entities, which are immunophenotypically related but clinically and histologically distinct.
Mutation in the TP53 gene in colorectal carcinoma detected by polymerase chain reaction
Authors: Han Eun‐Soo , Moyer Mary Pat , Naylor Susan , Sakaguchi Alan Y. 
Published: February 2007

AbstractThe human TP53 gene is a possible tumor suppressor since TP53 gene mutations are observed in >70% of sporadic colorectal carcinoma DNAs. In genomic DNAs from seven colon cancer cell samples, a 405 base pair DNA fragment containing exon 5, intron 5, and exon 6 of the TP53 gene was amplified by polymerase chain reaction and analyzed for mutations. One sample [human colon cancer (HCC) 278] was found to have a TP53 mutation altering the amino acid glutamine 167 in exon 5. A deletion of 2 bases changed glutamine 167 (CAG) to alanine (GCA) and the resulting frame‐shift produced an in‐frame stop codon at amino acid 179. While the normal TP53 gene gives rise to a 53 kD protein, the estimated size of this mutant TP53 protein if expressed would be approximately 20 kD.
Allelic 3p Deletions in High‐Grade Carcinomas After Transformation In Vitro of Human Uroepithelial Cells
Authors: Klingelhutz Aloysius J. , Wu Shi‐Qi , Bookland Elizabeth A. , Reznikoff Catherine A. 
Published: February 2007

AbstractRestriction fragment length polymorphism (RFLP) analysis for allelic losses on the chromosome arm 3p were performed on independent carcinomas produced in athymic nude mice after transformation in vitro of a pseudodiploid clonal SV40‐immortalized human uroepithelial cell line (SV‐HUC). We analyzed ten primary carcinomas with heterogeneous phenotypes for deletions on 3p by using three informative probes, D3S30, D3S2, and D3F15S2, which map to the 3p11‐p14, 3p21.1, and 3p21 regions, respectively. Five of the ten primary cancers showed reduction to homozygosity with at least one of the probes, and all five cancers were high‐grade and poorly differentiated. We also analyzed six carcinomas that arose after progression of low‐grade cancers, either spontaneously or after exposure to a human bladder carcinogen, to higher grades (progressed carcinomas). Four of the six exhibited 3p allelic loss. No preferential loss of a specific 3p allele was observed in any of the carcinomas. In addition, whereas most of the carcinomas showed allelic loss for all three of the probes, indicating a large‐scale deletion, several of the carcinomas exhibited losses for only one or two of the probes, thus making it possible, along with the cytogenetic data, to define the least common region of deletion to 3p13→p14.2. These results support the hypothesis that nonrandom loss of a gene or genes on 3p leads to the development of cancer. Furthermore, these findings associate deletion of a putative 3p13→p14.2 tumor suppressor gene region with the development of high‐grade uroepithelial carcinomas.
Characterization of Marker Chromosomes in Namalva Cells by Chromosomal In Situ Suppression (CISS) Hybridization and R‐Banding
Authors: Ruppersberger Peter , Arnold Michaela , Zankl Heinrich , Scherthan Harry 
Published: February 2007

AbstractChromosomal in situ suppression (CISS) hybridization was used to investigate the distribution of material of chromosomes 1 and 5 present in marker chromosomes of Namalva cells. The Namalva cell line, established from a Burkitt's lymphoma, exhibits a highly variable female karyotype with a large number of marker chromosomes. Libraries from sorted human chromosomes 1 and 5 were used to delineate material of these chromosomes present in the Namalva karyotype. We used the DAB/peroxidase reaction and reflection contrast microscopy for detection of biotinylated hybrid molecules. Identification of chromosomes was achieved by fluorescent R‐banding after CISS hybridization, which allowed the assignment of hybridized regions to the particular marker chromosomes. After CISS hybridization with a chromosome I library, the normal chromosome I was labelled as well as a large marker MI and the long arm of marker M3. Using a chromosome 5 library it could be shown that the distal part of the long arm of one chromosome 5 was translocated to marker M2. The normal chromosome 5 was completely labelled. The present investigation demonstrates the advantage of combining CISS hybridization and banding for the identification of complex, rearranged tumor karyotypes.
Gene Amplification and Gene Dosage in Cell Lines Derived From Squamous Cell Carcinoma of the Head and Neck
Authors: Yin Xiao‐Ying , Donovan‐Peluso Maryann , Whiteside Theresa L. , Johnson Jonas T. , Day Roger , Herberman Ronald B. , Locker Joseph 
Published: February 2007

AbstractGene amplification and related alterations in gene dosage were analyzed in a series of 34 cell lines derived from different human head and neck squamous cell carcinomas (SCCHN). INT2 gene amplification was observed in 62%, MYC gene amplification in 24%, and EGFR gene amplification in 21 % of the cell lines. There was a strong correlation between EGFR gene amplification and increased copies of the ERBB2 gene on chromosome 17, suggesting a synergistic selection for these two genes either during cancer progression or in culture. Two abnormalities showed a significant correlation with clinical course: MYC gene amplification showed an inverse correlation with tumor recurrence (r = ‐ 0.44, p = 0.01), and a small increase in MYCL gene copies on chromosome I correlated with the presence of metastases (r = 0.61, p = 0.001). This altered MYCL gene dosage might represent a chromosome translocation rather than true gene amplification. In addition to gene amplification, 79% of the cell lines had increased copies of chromosome 8. Comparison of the cell lines with several of the corresponding primary tumors demonstrated that most gene amplifications were already present in the primary tumors, although some appeared de novo in cell culture. These studies indicate that gene amplification, especially of INT2, is a prominent abnormality in head and neck squamous cell cancer. Aneuploidy and chromosomal lesions other than gene amplification were also found to alter the dosage of several oncogenes specifically.