bluuebunny/crossref_metadata_2025_split huggingface dataset:
Further cytogenetic characterization of multiple myeloma confirms that 14q32 translocations are a very rare event in hyperdiploid cases
Authors: Smadja Nicole Véronique , Leroux Dominique , Soulier Jean , Dumont Sylvie , Arnould Catherine , Taviaux Sylvie , Taillemite Jean Louis , Bastard Christian 
Published: September 2003

AbstractTranslocations involving the immunoglobulin heavy‐chain genes are frequent in multiple myeloma (MM), which can be separated into two groups according to the chromosome number pattern. 14q32 translocations 14q32t are more frequent in hypodiploid than in hyperdiploid karyotypes. However, conventional cytogenetics (CC) misses cryptic translocations, especially t(4;14)(p16;q32). Furthermore, recent interphase fluorescence in situ hybridization (FISH) studies found 14q32t in as many as 75% of MM cases. To identify in which CC group we failed to detect translocations, we designed a study by use of FISH with a dual‐color IGH probe on previously R‐banded metaphase cells, allowing the detection of both 14q32t and overall chromosomal abnormalities, in a new series of 55 MM with abnormal karyotypes: 4/29 hyperdiploid (14%) and 19/26 hypodiploid (73%) cases had a 14q32t. The t(4;14) was found in 2 hyperdiploid (7%) and 10 hypodiploid (39%) cases. We therefore confirm that 14q32t are much more frequent in hypodiploid than in hyperdiploid MM (P < 0.0001) and that cryptic t(4;14)(p16;q32) is strongly associated with hypodiploid karyotypes (P < 0.01). Through the use of this reliable assay, only 42% of MM had 14q32t. © 2003 Wiley‐Liss, Inc.
Expression profiling targeting chromosomes for tumor classification and prediction of clinical behavior
Authors: Lu Yong‐Jie , Williamson Daniel , Wang Rubin , Summersgill Brenda , Rodriguez Sandrine , Rogers Simon , Pritchard‐Jones Kathy , Campbell Colin , Shipley Janet 
Published: September 2003

AbstractTumors are associated with altered or deregulated gene products that affect critical cellular functions. Here we assess the use of a global expression profiling technique that identifies chromosome regions corresponding to differential gene expression, termed comparative expressed sequence hybridization (CESH). CESH analysis was performed on a total of 104 tumors with a diagnosis of rhabdomyosarcoma, leiomyosarcoma, prostate cancer, and favorable‐histology Wilms tumors. Through the use of the chromosome regions identified as variables, support vector machine analysis was applied to assess classification potential, and feature selection (recursive feature elimination) was used to identify the best discriminatory regions. We demonstrate that the CESH profiles have characteristic patterns in tumor groups and were also able to distinguish subgroups of rhabdomyosarcoma. The overall CESH profiles in favorable‐histology Wilms tumors were found to correlate with subsequent clinical behavior. Classification by use of CESH profiles was shown to be similar in performance to previous microarray expression studies and highlighted regions for further investigation. We conclude that analysis of chromosomal expression profiles can group, subgroup, and even predict clinical behavior of tumors to a level of performance similar to that of microarray analysis. CESH is independent of selecting sequences for interrogation and is a simple, rapid, and widely accessible approach to identify clinically useful differential expression. © 2003 Wiley‐Liss, Inc.
Molecular cloning of a constitutional t(7;22) translocation associated with risk of hematological malignancy
Authors: Hill Alexander S. , MacCallum Peter K. , Young Bryan D. , Lillington Debra M. 
Published: September 2003

AbstractWe report the molecular characterization of a reciprocal constitutional translocation t(7;22)(p13;q11.2) carried by three family members who have each developed a hematological malignancy. The chromosome 7 breakpoint was localized to a single BAC clone, RP11‐571N3, by sequential fluorescence in situ hybridization analysis of clones selected from the NCBI chromosome 7 map. This was further refined to a 739‐bp region by Southern blot analysis of DNA from the two cell lines 1193 and 1194 digested with EcoRI, HindIII, PstI, and PvuII. A 2.8‐kb fragment spanning the der(22) breakpoint was amplified by long‐range inverse PCR. The sequence of this fragment was used to predict the composition of the der(7) breakpoint, and a 1.3‐kb fragment was amplified by use of primers from both chromosomes 7 and 22 based on this prediction. The breakpoint on chromosome 22 is located between the 3rd and 4th V regions of the immunoglobulin lambda (IGL) locus, and the breakpoint on chromosome 7 is located 122 kb proximal to the insulin‐like growth factor binding protein (IGFBP) 3 gene. Examination of both reciprocal junctions showed that four bases were lost from chromosome 22, whereas 75 bases were lost from chromosome 7. Small insertions of 46 bases and 13 bases were found at the der(22) and the der(7) junctions, respectively. As a consequence of this event, the entire IGL locus, less the first three Vλ elements, is translocated to chromosome 7, whereas the three remaining Vλ elements on the der(22) are juxtaposed with IGFBP3 and IGFBP1. © 2003 Wiley‐Liss, Inc.
Clustering of hypermethylated genes in neuroblastoma
Authors: van Noesel Max M. , van Bezouw Saskia , Voûte P. A. , Herman James G. , Pieters Rob , Versteeg Rogier 
Published: September 2003

AbstractCpG‐island hypermethylation of gene promoters is a frequent mechanism for gene inactivation in tumors. Many neuroblastomas have hypermethylation and down‐regulation of CASP8, leading to resistance to tumor necrosis factor–related apoptosis‐inducing ligand (TRAIL). We recently found hypermethylation of the four TRAIL receptors in 9 neuroblastoma cell lines. Here, we analyzed methylation of 34 genes in 22 neuroblastoma cell lines. Of the 29 newly analyzed genes, only FLIP at chromosome band 2q33 was methylated in 8/22 cell lines. The FLIP protein is a negative regulator of Caspase 8. FLIP maps adjacent to CASP8, and their methylation patterns showed a moderate correlation. Furthermore, co‐methylation patterns were observed for the TRAIL receptor pairs DCR1 and DCR2 and between DR4 and DR5. All four receptors co‐localize in chromosome band 8p21. The 6 genes methylated in neuroblastomas appeared to occur in pairs. The genes within each pair have a strong sequence homology and originated from gene duplication. We found no evidence for regional spreading of methylation, given that we did not observe de novo methylation in additional local CpG islands. However, the gene pairs showed a striking co‐regulation at the mRNA expression level. Down‐regulation of FLIP strongly corresponds with down‐regulation of CASP8, and this was also found for DCR1 and DCR2. Only a subset of the down‐regulated genes was methylated. This suggests a mechanism of co‐regulated transcriptional silencing of the gene pairs, followed by a methylation event that is less penetrating. The methylation pattern therefore supports a model in which CpG islands are not randomly targeted by methylation in cancer. Specific transcriptional silencing probably marks genes that can become methylated. © 2003 Wiley‐Liss, Inc.
Aberrant expression of the LHX4 LIM‐homeobox gene caused by t(1;14)(q25;q32) in chronic myelogenous leukemia in biphenotypic blast crisis
Authors: Yamaguchi Mitsuko , Yamamoto Koh , Miura Osamu 
Published: September 2003

AbstractChromosomal aberrations observed in addition to the Philadelphia chromosome in chronic myelogenous leukemia (CML) are likely to be involved in disease progression to the blast crisis. We describe here a t(1;14)(q25;q32) as an additional chromosomal aberration in a patient with CML in biphenotypic blast crisis. By use of long‐distance inverse polymerase chain reaction (PCR), we cloned the chromosomal breakpoint and revealed that the immunoglobulin heavy chain gene is fused near its Eμ enhancer region to the 5′ region of the LHX4 LIM‐homeobox gene, whose expression is restricted to the central nervous system. By use of quantitative real‐time reverse‐transcription PCR, we found that the LHX4 mRNA is expressed at high levels in the patient's leukemic cells and in an acute lymphoblastic leukemia (ALL) cell line. The aberrant expression of the LHX4 gene by the t(1;14)(q25;q32) has very recently been reported in a case of ALL, thus, representing a rare, but recurrent genetic abnormality of possible importance in leukemogenesis. © 2003 Wiley‐Liss, Inc.
Development of a real‐time RT‐PCR assay for the quantification of the most frequent MLL/AF9 fusion types resulting from translocation t(9;11)(p22;q23) in acute myeloid leukemia
Authors: Scholl Claudia , Breitinger Heike , Schlenk Richard F. , Döhner Hartmut , Fröhling Stefan , Döhner Konstanze 
Published: September 2003

AbstractOne strategy to predict clinical outcome in patients with acute myeloid leukemia (AML) is detection of minimal residual disease (MRD) after achievement of hematologic complete remission (CR). We established a real‐time RT‐PCR assay by use of TaqMan technology for the identification of MRD by quantification of the most frequent fusion transcripts resulting from t(9;11)(p22;q23). To achieve comparable PCR efficiencies between the different PCR assays, primers were chosen to obtain amplicons of nearly identical lengths. MLL/AF9 copy numbers were normalized to the housekeeping gene porphobilinogen deaminase (PBGD). The sensitivity of the assay, as determined at the cellular level, was comparable to that of qualitative single‐round RT‐PCR. Samples from eight patients with t(9;11)‐positive AML were analyzed. At diagnosis and relapse, normalized copy numbers were positive and ranged from 490 to 5,558. Samples from two of seven patients collected at the time of CR became negative, whereas five cases still had positive normalized copy numbers with values between 5 and 5,286. The implications of MRD detection by MLL/AF9 fusion transcript quantification for the clinical management of t(9;11)‐positive AML have to be determined in further studies. © 2003 Wiley‐Liss, Inc.
Pattern of secondary genomic changes in pancreatic tumors of Tgfα/Trp53+/− transgenic mice
Authors: Schreiner Bettina , Baur Dorothee M. , Fingerle Alexander A. , Zechner Ulrich , Greten Florian R. , Adler Guido , Sipos Bence , Klöppel Günter , Hameister Horst , Schmid Roland M. 
Published: September 2003

AbstractTrp53+/− mice overexpressing Tgfα in a pancreas‐specific manner represent a well‐established animal model for pancreatic cancer. In this study we analyzed 38 pancreatic adenocarcinomas of these mice for secondary genomic changes by comparative genomic hybridization (CGH), loss of heterozygosity (LOH) analysis, real‐time PCR, and methylation‐specific analysis. CGH screening of the tumors revealed a recurrent pattern of genomic changes. In more than 50% of the tumors, chromosome 11 was affected. The gain of the proximal part spans about 16 cM, including the genes for Egfr, Rel, and Stk10. The distal part of chromosome 11, which contains the Trp53 locus, was deleted. LOH analysis proved that almost all tumors segregate the wild‐type Trp53 allele. The Cdkn2a locus on chromosome 4 was inactivated by hypermethylation in 55% of all tumors. In addition, two other changes were detected in a mutually exclusive manner: overrepresentation of part of chromosome 15, or more rarely, loss of the distal part of chromosome 14. Together these data suggest the induction of a uniform pattern of secondary genomic changes in this transgenic tumor model for pancreatic cancer. © 2003 Wiley‐Liss, Inc.
CDKN2A as a uveal and cutaneous melanoma susceptibility gene
Authors: Kannengiesser Caroline , Avril Marie‐Françoise , Spatz Alain , Laud Karine , Lenoir Gilbert M. , Bressac‐de‐Paillerets Brigitte 
Published: September 2003

AbstractA few families have been described whose members are affected by either cutaneous melanoma (CM) or uveal melanoma (UM), suggesting that a common susceptibility could exist. Although CDKN2A is the main CM predisposing gene, thus far no germline CDKN2A mutations have been described in families with both CM and UM. We report a Gly67Ser missense CDKN2A germline mutation in a melanoma‐prone family, where one carrier was affected by UM and the other by a CM. Immunohistochemistry performed on the UM tissue block revealed loss of CDKN2A protein staining in tumor cells. These observations demonstrate that CDKN2A is also a UM susceptibility gene. © 2003 Wiley‐Liss, Inc.
Compensatory cortical activation observed by fMRI during a cognitive task at the earliest stage of multiple sclerosis
Authors: Audoin Bertrand , Ibarrola Danielle , Ranjeva Jean‐Philippe , Confort‐Gouny Sylviane , Malikova Irina , Ali‐Chérif André , Pelletier Jean , Cozzone Patrick 
Published: September 2003

AbstractRecent functional magnetic resonance imaging (fMRI) studies have suggested that functional cortical changes seen in patients with early relapsing‐remitting multiple sclerosis (MS) can have an adaptive role to limit the clinical impact of tissue injury. To determine whether cortical reorganization occurs during high cognitive processes at the earliest stage of multiple sclerosis (MS), we performed an fMRI experiment using the conventional Paced Auditory Serial Addition Test (PASAT) as paradigm in a population of ten patients with clinically isolated syndrome suggestive of multiple sclerosis (CISSMS). At the time of the fMRI exploration, mean disease duration was 6.8 ± 3.3 months. We compared these results to those obtained in a group of ten education‐, age‐, and sex‐matched healthy controls. Subjects were explored on a 1.5 T MRI system using single‐shot gradient‐echo EPI sequence. Performances of the two groups during PASAT recorded inside the MR scanner were not different. Statistical assessment of brain activation was based on the random effect analysis (between‐group analysis two‐sample t‐test P < 0.005 confirmed by individual analyses performed in the surviving regions P < 0.05 Mann Whitney U‐test). Compared to controls, patients showed significantly greater activation in the right frontopolar cortex, the bilateral lateral prefrontal cortices, and the right cerebellum. Healthy controls did not show greater activation compared to CISSMS patients. The present study argues in favor of the existence of compensatory cortical activations at the earliest stage of MS mainly located in regions involved in executive processing in patients performing PASAT. It also suggests that fMRI can evidence the active processes of neuroplasticity contributing to mask the clinical cognitive expression of brain pathology at the earliest stage of MS. Hum. Brain Mapping 20:51–58, 2003. © 2003 Wiley‐Liss, Inc.
Urinary IL‐2 assay for monitoring intravesical bacillus Calmette‐Guérin response of superficial bladder cancer during induction course and maintenance therapy
Authors: Saint Fabien , Kurth Nathalie , Maille Pascale , Vordos Dimitri , Hoznek Andre , Soyeux Pascale , Patard Jean Jacques , Abbou Claude C. , Chopin Dominique K. 
Published: September 2003

AbstractWe evaluated the clinical significance of Th1(IL‐2)/Th2(IL‐10) urinary profiles during a weekly induction course lasting 6 weeks, followed by a weekly maintenance therapy schedule for 3 weeks. Urinary IL‐2 and /IL‐10 were measured by ELISA in 39 patients receiving BCG for superficial bladder cancer or carcinoma in situ. Measurements were made after each instillation of 81 mg of BCG Connaught (Immucyst) during the induction course and the 3‐week maintenance therapy (given at 3, 6, 12, 18, 24, 30 and 36 months). Cytokine levels were correlated with the risk of recurrence, progression, leukocyturia and adverse events. Median follow‐up was 35 months (range 7–72 months). Complete responses to BCG were obtained in 30 patients (77%); the remaining 9 patients relapsed (23%), and 4 of these patients progressed (10.2%). Failure to detect urinary IL‐2 during BCG induction course and the first extended induction cycle (6+3 schedule) correlated with time to recurrence (p = 0.01) and progression (p = 0.01). During the extended induction cycle, the first instillation was associated with an IL‐2 cytokine profile, whereas the second and third instillations were associated with a switch to an IL‐10 cytokine profile. This switch was associated with leukocyturia (p = 0.0001) and adverse events (p = 0.03). The 6+3 schedule is associated with urinary IL‐2 overproduction and improved recurrence‐ and progression‐free survival. During the BCG extended induction cycle, the favorable IL‐2 urinary cytokine pattern gradually switches to an IL‐10 profile, suggesting that the schedule based on 3 weekly instillations may be unsuitable for some patients and that the dose and frequency of maintenance BCG instillations may be adapted to individual urinary cytokine levels. © 2003 Wiley‐Liss, Inc.
Tobacco smoking and chewing, alcohol drinking and lung cancer risk among men in southern India
Authors: Gajalakshmi Vendhan , Hung Rayjean J. , Mathew Aleyamma , Varghese Cherian , Brennan Paul , Boffetta Paolo 
Published: September 2003

AbstractIn India, lung cancer is one of the most common and lethal cancers, and tobacco smoking remains its most important etiologic factors. The objective of our study is to examine the effects of different tobacco consumption forms, including smoking and chewing, on lung cancer risk of men in southern India, especially to compare the effects of bidi smoking to cigarette smoking on lung carcinogenesis. We also evaluated the possible role of Indian alcohol beverages and non‐Indian alcohol beverages on lung carcinogenesis. We conducted a case‐control study in Chennai and Trivandrum. In total, 778 lung cancer cases and 3,430 controls, including 1,503 cancer controls and 1,927 healthy controls, were recruited. The effects of cigarette, bidi smoking, chewing and alcohol drinking on the risk of lung cancer were estimated from unconditional multivariate logistic regression. We also applied the generalized additive model (GAM) with locally‐weighted running‐line smoothers (loess) to find the most plausible curve for the dose‐response relationship. The results from GAM suggest a plateau after 35 years of smoking or 10 cigarette‐equivalent pack‐years for both cigarette and bidi. The OR is 4.54 (95%CI=2.96–6.95) and 6.45 (95%CI=4.38–9.50) for more than 30 years of cigarette‐only and bidi‐only smoking, respectively, and 6.87 (95%CI=4.62–10.2) and 10.7 (95%CI=5.82–19.6) for more than 12 weighted cumulative cigarette‐only and bidi‐only consumption, respectively. The lung cancer risk of former cigarette smokers drops down more quickly after quitting smoking compared to former bidi smokers. There is no evidence for the effect of chewing and lung cancer risk nor clear evidence of an effect of overall alcohol drinking among never‐smokers, although Indian alcohol drinking seemed to remain associated with lung cancer risk under limited power (OR=2.67, 95%CI=1.02–7.02). Bidi smoking seems to have a stronger carcinogenic effect than cigarette smoking: this difference holds no matter which aspect of smoking was considered. © 2003 Wiley‐Liss, Inc.
Infrequent microsatellite instability in liver fluke infection‐associated intrahepatic cholangiocarcinomas from Thailand
Authors: Liengswangwong Upama , Nitta Takayuki , Kashiwagi Hironobu , Kikukawa Hiroko , Kawamoto Toru , Todoroki Takeshi , Uchida Kazuhiko , Khuhaprema Thiravud , Karalak Anant , Srivatanakul Petcharin , Miwa Masanao 
Published: September 2003

AbstractThe liver fluke infection‐associated intrahepatic cholangiocarcinoma (ICC) is a major liver cancer in Northeast Thailand. The molecular basis of this ICC is poorly understood. To address possible roles of the DNA mismatch repair (MMR) system in ICC carcinogenesis, a fluorescence‐labeling PCR/laser scanning technique with high sensitivity was employed to analyze genomic instability in the nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) in 24 fresh and 13 formalin‐fixed, paraffin‐embedded tissues of ICC and their corresponding normal parts. Microsatellite instability (MSI) was assessed in nDNA, using 12 highly polymorphic loci including 5 Bethesda markers. These loci were mainly related to major MMR genes, hMSH2 and hMLH1. Also 3 (C)n and/or (C)n(A)n repeat instability at 1 noncoding region in the displacement‐loop (D‐loop) and 2 coding sequences in NADH dehydrogenase subunit 1 and subunit 5 gene in mtDNA were analyzed. MSI was only detected in 1 (2.7%), 6 (16.7%), 1 (2.9%), 1 (2.9%) or 2 (6.3%) out of 37, 36, 35, 35 or 32 cases at BAT‐25, D2S123, D3S1611, D11S904 or D17S250, respectively. LOH was found at D3S1298, D3S1561, D5S346 and TP53 in 4 (18.2%) out of 22, 2 (18.2%) out of 11, 6 (33.3%) out of 18 and 3 (12.5%) out of 24 informative cases, respectively. In mtDNA, none except a single case out of the 37 (2.7%) exhibited repeat sequence instability in the D‐loop. We conclude that the liver fluke infection‐associated ICC in Thailand is classified as low frequency MSI or microsatellite stable type and that DNA MMR system, through hMSH2 and hMLH1 gene mutations, does not play a major role in its carcinogenesis. © 2003 Wiley‐Liss, Inc.
Prevalence and physical status of human papillomavirus in squamous cell carcinomas of the head and neck
Authors: Koskinen Walter J. , Chen Ren Wei , Leivo Ilmo , Mäkitie Antti , Bäck Leif , Kontio Risto , Suuronen Riitta , Lindqvist Christian , Auvinen Eeva , Molijn Anco , Quint Wim G. , Vaheri Antti , Aaltonen Leena‐Maija 
Published: September 2003

AbstractFresh‐frozen biopsies were obtained from 61 patients at diagnosis of squamous cell carcinoma of the head and neck (HNSCC) for study of the prevalence and physical status of human papillomavirus (HPV) DNA. The frequency of HPV DNA and genotypes were determined by SPF10 PCR screening with a general probe hybridization and INNO‐LiPA HPV genotyping assay. In addition, a single‐phase PCR with primers FAP 59/64 and a nested PCR with primers CP 65/70 and CP 66/69 served to detect particularly cutaneous HPV types. By the sensitive SPF10 PCR and INNO‐LiPA assay, 37 of 61 (61%) samples were positive for HPV. HPV‐16 was the most frequently detected type (31 of 37, 84%). Multiple infections were found in 8 of 37 (22%) of the HPV‐positive samples, and co‐infection by HPV‐16 and HPV‐33 was predominant. No cutaneous HPV types were detected. Patients with HPV‐positive tumors had similar prognosis as those with HPV‐negative ones. Real‐time PCR analysis of the HPV‐16 positive samples indicated the presence of integrated (11 of 23, 48%), episomal (8 of 23, 35%) and mixed forms (4 of 23, 17%) of HPV DNA. The viral load of HPV DNA exhibited large variation. The median copy numbers of E6 DNA in tonsillar specimens were approximately 80,000 times higher than that in nontonsillar HNSCC ones. Patients with episomal viral DNA were more frequently found to have large (T3–T4) tumors at diagnosis than were those with integrated or mixed forms. © 2003 Wiley‐Liss, Inc.