bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cytogenetic studies of breast carcinomas: Different karyotypic profiles detected by direct harvesting and short‐term culture
Authors: Steinarsdóttir Margrét , Pétursdóttir Ingibjörg , Snorradóttir Steinunn , Eyfjörd Jórunn E. , Ögmundsdóttir Helga M. 
Published: February 2007

AbstractChromosome analysis was performed on samples from 85 consecutive patients with breast cancer by one or more of three different methods: direct harvest, culture after mechanical disaggregation, and culture after collagenase digestion. Metaphases suitable for karyotyping were obtained in 70% of the cases; direct harvest yielded metaphases in 29% and cultures without and with digestion in 40% and 59%, respectively. Chromosomal abnormalities were detected in 37 cases. Cells judged to be phenotypically abnormal in culture were twice as likely to reveal chromosomal aberrations as normal‐looking cells. Eight cases showed multiclonal abnormalities. Significant differences were detected in the karyotypic profile depending on the method used. With direct harvest, the yield of complex chromosomal changes was 87%, compared to 44% after culture of digested tissue (P < 0.01), and also polyploidy was more common in direct‐harvested samples. Detailed karyotypic analysis was possible in 29 primary tumors. The chromosomes most frequently involved were 1, 3, 7, 11, 16, and 17. Recurrent structural abnormalities were der( 1; 16) (q 10; p 10), i(1)(q10), del(6)(q21), and del(1)(p22). Breakpoints clustered to the cententromere regions of chromosomes 1, 3, 11, 15, and 16 and to the short arms of chromosomes 7, 17, and 19. Seven of twenty‐nine fully analyzed cases had a family history of breast cancer, and changes of chromosomes 1, 3, and 15 seemed to be more common in these cases. There was an association between karyotype and survival: The 3 year survival was 63% in patients with complex karyotypic changes and 92% in those without complex changes. © 1995 Wiley‐Liss, Inc.
Allelic imbalance in gastric cancer: An affected site on chromosome arm 3p
Authors: Schneider Barbara G. , Pulitzer Donald R. , Brown Rhonda D. , Prihoda Thomas J. , Bostwick David G. , Saldivar Victor , Rodriguez‐Martinez Hector A. , Gutiérrez‐Diaz C. M. Esther , O'Connell Peter 
Published: February 2007

AbstractIn order to detect regions of DNA containing tumor suppressor genes involved in the development of gastric cancer, we performed an allelotype study on 78 gastric adenocarcinomas from a population composed largely of Texan Hispanics and Anglos, two ethnic groups that have a ratio of incidence rates of gastric cancer of approximately 2: 1. In total, 42 microsatellite markers were employed, which detected at least one site per arm of each autosome in the human genome. These included several markers linked to known tumor suppressor genes (TP53, APC, DCC, RBI, and BRCAI). Sites showing quantitative allelic imbalance (Al) greater than 30% were located on 3p (36%), 11q (31%), 12q (38%), 13q (33%), 17p near TP53 (74%), and 17q near BRCAI (32%). Among the 22% of cases showing microsatellite instability (MI), a subset (4 of 17) showed instability at 59% or more of sites tested. No ethnic bias was detected in cases showing MI or in cases with Al at sites with rates of AI above 30%. Tumors of the intestinal subtype were significantly more likely than diffuse tumors to show AI at D 135170 (P = 0.01). A deletion map of chromosome arm 3p was prepared for tumors with Al at D3S1478. These data indicate that a tumor suppressor gene on chromosome arm 3p is involved in the development of a subset of gastric cancers. © 1995 Wiley‐Liss, Inc.
Molecular analysis of genetic changes in ependymomas
Authors: Bijlsma Emilia K. , Voesten Annet M. J. , Bijleveld Engelien H. , Troost Dirk , Westerveld Andries , Mérel Philippe , Thomas Gilles , Hulsebos Theo J. M. 
Published: February 2007

AbstractEpendymomas are glial cell‐derived tumors. They are, in contrast to other gliomas (astrocytomas, oligodendrogliomas, and oligoastrocytomas), ill‐defined with respect to the genes and chromosomal segments important in their tumorigenesis. In this study, we extensively screened I7 ependymomas for genetic changes characteristic of other gliomas. Allelic loss was detected on chromosome arm 22q in three tumors; on chromosome 10 in two tumors; on chromosome arm 17p in two tumors; and on chromosome arms 6q, 9p, I 3q, and I9q, each in one tumor. No allelic losses were found on chromosome arms I p and I6q. None of the tumors had EGFR gene amplification. In each case, the chromosomal segment affected by the deletion included the region known t o harbor a tumor suppressor gene important in glioma tumorigenesis. We conclude that ependymomas resemble the other glial neoplasms with respect to type and location of the chromosomal changes involved. Given the relatively infrequent occurrence of these genetic changes, ependymomas should be considered genetically as low‐grade gliomas. © 1995 Wiley‐Liss, Inc.
Loss of Chromosome 17 loci in prostate cancer detected by polymerase chain reaction quantitation of allelic markers
Authors: Brothman Arthur R. , Steele Michael R. , Williams Briana J. , Jones Emma , Odelberg Shannon , Albertsen Hans M. , Jorde Lynn B. , Rohr L. Ralph , Stephenson Robert A. 
Published: February 2007

AbstractUsing a polymerase chain reaction/microsatellite marker system, we demonstrated that 6 of 22 (27%) clinical stage B (early) primary prostate tumors showed loss of heterozygosity at one or more of five loci on chromosome 17. The sensitivity of this study was increased by use of a Phosphorlmager and statistical analysis of replicate tumor‐normal DNA pairs. Two patients showed tumor‐specific interstitial loss at a locus in close proximity to the familial breast cancer gene BRCAI. These findings suggest that genes on the proximal long arm of chromosome I7 play a pivotal role in the early development of at least a subset of prostatic tumors. © 1995 Wiley‐Liss, Inc.
Loss of heterozygosity in the tuberous sclerosis (TSC2) region of chromosome band l6p13 occurs in sporadic as well as TSC‐associated renal angiomyolipomas
Authors: Henske Elizabeth Petri , Neumann Hartmut P. H. , Scheithauer Bernd W. , Herbst Eberhard W. , Short M. Priscilla , Kwiatkowski David J. 
Published: February 2007

AbstractAngiomyolipomas (AMLs) are renal tumors that occur both sporadically and in association with tuberous sclerosis (TSC). TSC is an autosomal dominant disorder characterized by hamartomatous lesions in multiple organs. Two TSC loci are recognized TSCl on 9q34 and TSC2 on 16pl3. Loss of heterozygosity (LOH) at the TSCI and TSC2 loci in lesions from TSC patients has recently been reported. Lesions that are not associated with TSC have not been previously examined for LOH at the TSC loci. We analyzed 29 renal angiomyolipomas from patients without a history of TSC. Three tumors demonstrated LOH on I6p 13. This is the first report indicating that mutations in TSC2 occur in tumors of patients who do not have TSC. We also found LOH on I6p 13 in 5 of 8 TSC‐associated AMLs. Two of these tumors were from a single patient and demonstrated different regions of LOH. These findings support the hypothesis that the TSC2 gene functions as a tumor suppressor.
Comparative genomic hybridization analysis of human sarcomas: I. Occurrence of genomic imbalances and identification of a novel major amplicon at 1q21–q22 in soft tissue sarcomas
Authors: Forus Anne , Weghuis Daniël Olde , Smeets Dominique , Fodstad Øystein , Myklebost Ola , van Kessel Ad Geurts 
Published: February 2007

AbstractComparative genomic hybridization (CGH) was recently developed as a tool to survey entire genomes for variations in DNA sequence copy numbers. We have applied this technique to detect and map amplified regions in 54 soft tissue sarcomas. Aberrations were detected by visual analysis of hybridizations or contrast‐enhanced digital images, followed by quantitative digital ratio imaging of the aberrant chromosomes. Several tumors showed increased DNA sequence copy number at 12q14, as expected. However, CGH analysis detected amplification of 12q14 also in some tumors where neither MDM2 nor CDK4 was amplified, suggesting that another as yet unknown gene(s) may drive amplification of this region in sarcomas. Furthermore, a novel recurring amplicon was detected at 1q21‐q22. DNA amplifications coinciding with this segment were as frequent as those observed for 12q14, indicating that 1q21‐q22‐linked gene(s) may also play an important role in the development and/or progression of human soft tissue sarcomas.
Comparative genomic hybridization analysis of human sarcomas: II. Identification of novel amplicons at 6p and 17p in osteosarcomas
Authors: Forus Anne , Weghuis Daniël Olde , Smeets Dominique , Fodstad Øystein , Myklebost Ola , van Kessel Ad Geurts 
Published: February 2007

AbstractUsing comparative genomic hybridization (CGH), we have identified and mapped regions of DNA amplification in primary and metastatic osteosarcomas. Samples were obtained from four patients and ten independent xenografts. Sixty‐four percent of the tumors showed increased DNA‐sequence copy numbers, affecting 23 different chromosomal sites. Most of these regions were not previously associated with the development and/or progression of these tumors. Amplicons originating from 1q21–q23, 6p, 8q23‐qter, and 17p11‐p12 were observed most frequently. The 6p and 17p11–p12 amplicons seem to be specific for osteosarcomas, indicating that these regions may harbor genes relevant for the development of these tumors.
Identification of two distinct regions of deletion at 6q in gastric carcinoma
Authors: Queimado Lurdes , Seruca Raquel , Costa‐Pereira Altamiro , Castedo Sérgio 
Published: February 2007

AbstractLoss of heterozygosity (LOH) affecting the long arm of chromosome 6 has been found repeatedly in human cancers. Recently, our group reported that del(6)(q21‐22→qter) was the most consistent structural cytogenetic abnormality in gastric carcinomas. To determine more precisely the deleted region, we studied 51 tumors with 9 polymorphic markers on this chromosome arm. LOH of one or more markers was found in 39% of the tumors. LOH at region 6q22.3 was detected in 50% of informative tumors and at 6q26‐q27 in 37% of informative tumors. By comparative analysis of LOH regions, we identified two separate regions of overlapped deletions at 6q, one between 6q16.3‐q21 and 6q22.3‐q23.1, another distal to 6q23‐q24. A comparison of clinicopathologic features of gastric carcinomas with and without LOH at 6q revealed statistically significant or suggestive differences between LOH and young age of the patients and proximal location of the tumors. The two informative early gastric carcinomas both showed LOH at 6q. The occurrence of LOH at 6q was similar in all histological types. We conclude that two distinct regions at 6q appear to be involved in the early stages of gastric carcinogenesis.
Balanced translocation in a neuroblastoma patient disrupts a cluster of small nuclear RNA UI and tRNA genes in chromosomal band Ip36
Authors: van der Drift Pauline , Chan Alvin , Laureys Geneviève , van Roy Nadine , Sickmann Grace , den Dunnen Johan , Westerveld Andries , Speleman Frank , Versteeg Rogier 
Published: February 2007

AbstractChromosomal band Ip36 probably harbours several neuroblastoma suppressor genes. A neuroblastoma patient has been described with a constitutional balanced translocation, t(1;17)(p36;q12‐21). Cytogenetically, no loss of chromosomal material was visible. The Ip36 translocation breakpoint could therefore have inactivated one allele of a tumour suppressor gene, thus predisposing the patient to develop neuroblastoma. We localized this breakpoint by pulsed field gel electrophoresis, analysis of yeast artificial chromosomes, and fluorescence in situ hybridization. Here we report that the breakpoint is within a large cluster of small nuclear RNA U1 (RNU1) and some tRNA genes (TRE, TRN) on chromosomal band 1p36. The size of this cluster is over two megabases and it contains many other locally repeated sequences. Polyadenylated transcripts were identified for some of these sequences. In addition, the cluster is the target for integration of an adenovirus 5/SV40 hybrid virus. The translocation breakpoint maps distal of this viral integration site and proximal of marker PND.
Fluorescence in situ hybridization analysis of whole‐arm 7;12 translocations in hematologic malignancies
Authors: Johansson Bertil , Arheden Kristina , Höglund Mattias , Othzén Annika , Békássy Albert N. , Turesson Ingemar , Heim Sverre , Mitelman Felix 
Published: February 2007

AbstractCytogenetic analysis of one case of acute myeloid leukemia (AML), one of acute lymphoblastic leukemia (ALL), one of refractory anemia with excess of blasts (RAEB), and one of acute mixed lineage leukemia (AMLL) with unbalanced 7;12 translocations mapped the breakpoints to the centromeres on both chromosomes. The rearrangements were interpreted as the whole‐arm translocations der(7;12)(q10;q10) in the AML and ALL and der(7;12)(p10;q10) in the RAEB and AMLL. However, further analysis by metaphase and/or interphase fluorescence in situ hybridization (FISH) showed centric fusion only in the AML and ALL. In the RAEB and AMLL, centromeric material from chromosome 7 but not from 12 was present in the derivative chromosome. Whereas the t(7;12) resulted in loss of 12p in all four cases, the corresponding chromosome 7 imbalances differed—monosomy for 7q in the RAEB and AMLL and monosomy for 7p in the AML and ALL. Six hematologic neoplasms with unbalanced whole‐arm or near‐centromeric 7;12 translocations and seven dic(7;12) with juxtacentromeric breakpoints have been reported previously: 2 AML, 1 RAEB in transformation, and 10 ALL. All karyotypically informative cases had loss of 12p material. All but one of the cases with combined 7p and 12p deletion were ALL, whereas all cases with 7q and 12p loss showed myeloid differentiation. No particular clinical, morphologic, or immunophenotypic features seem to characterize ALLs with t(7;12). AMLs with an unbalanced t(7;12), often together with 5q deletions, might be associated with previous genotoxic exposure and poor prognosis.
Mitochondrial ATP synthase α‐subunit gene amplified in a retinoblastoma cell line maps to chromosome 18
Authors: Bie Wenjun , Squire Jeremy A. , Fraser Murray , Paterson Malcolm C. , Godbout Roseline 
Published: February 2007

AbstractThe human retinoblastoma cell line Y79 has multiple copies of the MYCN gene and the DEAD box gene DDX1. Both genes have been mapped to chromosome band 2p24. A third gene, encoding the α‐subunit of mitochondrial ATP synthase (ATPSA), is also amplified in Y79. Here we report that there are at least four human mitochondrial ATPSA‐related genes located on four different chromosomes. The ATPSA gene that is amplified in Y79 originates from chromosome 18. In Y79, the amplified copies of both the ATPSA and the MYCN genes are located on a homogeneously staining region (HSR) at chromosome band 1p34.
TP53 mutations and breast cancer prognosis: Particularly poor survival rates for cases with mutations in the zinc‐binding domains
Authors: Børresen Anne‐Lise , Andersen Tone Ikdahl , Eyfjörd Jorunn E. , Cornelis Renee S. , Thorlacius Steinunn , Borg Åke , Johansson Ulla , Theillet Charles , Scherneck Siegfried , Hartman Susanne , Cornelisse Cees J. , Hovig Eivind , Devilee Peter 
Published: February 2007

AbstractAcquired mutations in TP53 as well as immunohistochemically detectable protein expression have been implicated as prognostic factors for breast cancer. We have evaluated the relationship between mutations detected in 119 breast tumours and various clinicohistopathological indices, stratifying the mutations according to the functional domains as defined by the recent elucidation of the crystal structure of the protein. Patients with missense mutations located in regions encoding parts of the protein involved in zinc‐binding had significantly decreased disease‐free and overall survival relative to patients whose tumours had mutations in other domains. These results indicate that these biochemically defined domains also have biological relevance in terms of breast cancer disease course, and suggest that some mutations in TP53, more than others, can contribute to the development of clinically more aggressive and perhaps treatment resistant breast tumours. When confirmed, this will be of potential importance in predicting the clinical behaviour of breast cancer and its responsiveness to therapy.
Complex MLL rearrangement in a patient with T‐cell acute lymphoblastic leukemia
Authors: Chervinsky David S. , Sait Sheila N. J. , Nowak Norma J. , Shows Thomas B. , Aplan Peter D. 
Published: February 2007

AbstractMLL (also known as ALL‐1, HTRX, or HRX) gene translocations are among the most common chromosomal abnormalities recognized in both B‐lineage acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). However, MLL gene rearrangements are uncommon in T‐cell ALL. We recently detected an MLL gene rearrangement in a patient with typical T‐cell ALL (CD2+, CD4+, CD5+, CD7+, CD8+, HLA DR−) and an apparently normal karyotype (46.XX). The rearrangement was cloned and characterized; a DNA fragment distal to the breakpoint was mapped by fluorescence in situ hybridization (FISH) to 19p13, indicating that the leukemic blasts had undergone a cytogenetically undetected rearrangement involving chromosomes 11 and 19. A reverse transcriptase‐polymerase chain reaction (RT‐PCR) assay demonstrated an in‐frame fusion mRNA between the amino terminus of MLL and the carboxy terminus of ENL (also known as MLLT1 or LTG19), a gene that has been mapped to 19p13. In addition, MLL sequences distal (telomeric) to the breakpoint were deleted from the genome, which precludes the formation of a reciprocal ENL/MLL fusion protein. These findings suggest that an MLL/ENL fusion protein (and not a reciprocal ENL/MLL fusion) was likely to be pathogenic in this patient, and they reinforce previous studies showing that leukemic blasts with apparently normal karyotype may harbor MLL rearrangements. Additionally, this report provides the first conclusive evidence of an MLL/ENL gene fusion characterized at a molecular level in a patient with T‐cell ALL.
Chromosomes in gliomatosis cerebri
Authors: Hecht Barbara K. , Turc‐Carel Claude , Chatel Marcel , Lonjon Michel , Roche Jean Luc , Gioanni Janine , Hecht Frederick , Gaudray Patrick 
Published: February 2007

AbstractGliomatosis cerebri is a rare brain tumor which histologically resembles a diffuse cerebral astrocytoma. It can simultaneously infiltrate multiple sites in the cerebrum, cerebellum, brainstem, and spinal cord. This remarkable diffuseness has led to the idea that gliomatosis cerebri does not derive from a solitary focus but must arise from a broad field of glial cells. We studied the chromosomes from gliomatosis cerebri in a 12‐year‐old boy by conventional cytogenetics and fluorescence in situ hybridization (FISH). Aside from normal cells, we found a majority of cells with the karyotype 44,XY,del(6)(q25),del(14)(q21), der(15;21)(q10;q10),add(18)(q22),del(19)(p12),add(20)(p13), ‐21. A smaller proportion of cells had 88 chromosomes with a doubling of this abnormal karyotype. These findings are consistent with a clonal neoplasm stemming from a single cell. The chromosome changes we observed, with the possible exception of the chromosome 6 deletion, did not resemble those frequently found in astrocytomas. Gliomatosis cerebri may therefore belong to a separate category of brain tumors.
Identification of amplified DNA sequences in breast cancer and their organization within homogeneously staining regions
Authors: Muleris Martine , Almeida Anna , Gerbault‐Seureau Michèle , Malfoy Bernard , Dutrillaux Bernard 
Published: February 2007

AbstractA modified comparative genomic hybridization (mCGH) technique was used to identify and map amplified DNA sequences in six homogeneously staining regions (hsr) from three primary breast carcinomas. Five different chromosomal regions and bands were identified as sites of amplification: 8p1, 17q21.1, 17q23 (two cases), 19q13.3, and 20q13.3. The mCGH site located on 17q21.1 was demonstrated to correspond to a 50–100‐fold amplification of ERBB2. Further in situ hybridization experiments were used to confirm the mCGH results and to characterize the organization of the amplified sequences within the hsr. In five of six instances, two or more chromosomal regions were found amplified in the same hsr. In the tumor with the less modified karyotype, the two hsr comprised DNA sequences from three different chromosomes and showed different patterns of amplification. In the tumor with the most rearranged karyotype, the hsr‐carrying chromosomes were formed by the translocation and amplification of sequences from three or four different chromosomal sites. This illustrates the complexity of the amplification process in breast cancers.
Alterations of CDKN2 (p16) in non‐small cell lung cancer
Authors: Vos Sven De , Miller Carl W. , Takeuchi Seisho , Gombart Adrian F. , Cho Steve K. , Koeffler H. Phillip 
Published: February 2007

AbstractThe cyclin‐dependent kinase inhibitor known as p16 (CDK41, CDKN2, INK4A, MTS1) has been proposed as a tumor suppressor gene on chromosome segment 9p21. We have evaluated CDKN2 alterations in 34 non‐small cell lung cancers (NSCLCs) with matched normal tissue controls and in 9 NSCLC cell lines by Southern blotting, single‐strand conformation polymorphism (SSCP) with the polymerase chain reaction, and direct sequencing. In addition, loss of heterozygosity at chromosome segment 9p21, with the use of the microsatellite marker D9S171, was studied in these samples. Whereas CDKN2 was either deleted or mutated in NSCLC cell lines at a high frequency (6/9, 67%), alterations were much less frequent (7/34, 21%) in primary tumor samples. Only one sample contained a point mutation in exon 1 of CDKN2. In addition, two samples had homozygous deletions of CDKN2 in exon 1; one had a homozygous and three a hemizygous deletion of exon 2. Possibly normal tissue contaminating our tumor samples may have masked homozygous deletions in these cases. Four patient samples had LOH in the region of CDKN2 on chromosome segment 9p21; two of these samples had potentially inactivating alterations of CDKN2; one sample had a mutation of CDKN2, and the other had a homozygous deletion of exon 1. In summary, inactivation of CDKN2 is implicated in the development of about 20% of NSCLC, but the possibility of another tumor suppressor gene on chromosome segment 9p21 important in lung cancer cannot be eliminated.
Allelic imbalance study of 16q in human primary breast carcinomas using microsatellite markers
Authors: Dorion‐Bonnet F. , Mautalen S. , Hostein I. , Longy M. 
Published: February 2007

AbstractThe high incidence of allelic imbalance on the long arm of chromosome 16 in breast cancer suggests its involvement in the development and progression of the tumor. Several loss of heterozygosity (LOH) studies have led to the assignment of commonly deleted regions on 16q where tumor suppressor genes may be located. The most recurrent LOH regions have been 16q22.1 and 16q22.4‐qter. The aim of this study was to gain further insight into the occurrence of one or multiple “smallest regions of overlap” on 16q in a new series of breast carcinomas. Hence, a detailed allelic imbalance map was constructed for 46 sporadic breast carcinomas, using 11 polymorphic microsatellite markers located on chromosome 16. Allelic imbalance of one or more markers on 16q was shown by 30 of the 46 tumors (65%). Among these 30 carcinomas, LOH on the long arm of chromosome 16 was detected at all informative loci in 19 (41%); 13 of them showed allelic imbalance on the long but not on the short arm, with the occurrence of variable “breakpoints” in the pericentromeric region. The partial allelic imbalance in 11 tumors involved either the 16q22.1‐qter LOH region or interstitial LOH regions. A commonly deleted region was found between D16S421 and D16S289 on 16q22.1 in 29 of the 30 tumors. The present data argue in favor of an important involvement of a tumor suppressor gene mapping to 16q22.1 in the genesis or progression of breast cancer.