bluuebunny/crossref_metadata_2025_split huggingface dataset:
21q22 balanced chromosome aberrations in therapy‐related hematopoietic disorders: Report from an International Workshop†
Authors: Slovak Marilyn L. , Bedell Victoria , Popplewell Leslie , Arber Daniel A. , Schoch Claudia , Slater Rosalyn 
Published: August 2002

AbstractThe International Workshop on the relationship between prior therapy and balanced chromosome aberrations in therapy‐related myelodysplastic syndromes (t‐MDS) and therapy‐related acute leukemia (t‐AL) identified 79 of 511 (15.5%) patients with balanced 21q22 translocations. Patients were treated for their primary disease, including solid tumors (56%), hematologic malignancy (43%), and juvenile rheumatoid arthritis (single case), by radiation therapy (5 patients), chemotherapy (36 patients), or combined‐modality therapy (38 patients). 21q translocations involved common partner chromosomes in 81% of cases: t(8;21) (n = 44; 56%), t(3;21) (n = 16; 20%), and t(16;21) (n = 4; 5%). Translocations involving 15 other partner chromosomes were also documented with involvement of AML1(CBFA2/RUNX1), identifying a total of 23 different 21q22/AML1 translocations. The data analysis was carried out on the basis of five subsets of 21q22 cases, that is, t(8;21) with and without additional aberrations, t(3;21), t(16;21), and other 21q22 translocations. Dysplastic features were present in all 21q22 cases. Therapy‐related acute myeloid leukemia (t‐AML) at presentation was highest in t(8;21) (82%) and lowest in t(3;21) (37.5%) patients. Cumulative drug dose exposure scores for alkylating agents (AAs) and topoisomerase II inhibitors indicated that t(3;21) patients received the most intensive therapy among the five 21q22 subsets, and the median AA score for patients with secondary chromosome 7 aberrations was double the AA score for the entire 21q22 group. All five patients who received only radiation therapy had t(8;21) t‐AML. The median latency and overall survival (OS) for 21q22 patients were 39 and 14 months (mo), compared to 26 and 8 mo for 11q23 patients, 22 and 28 mo for inv(16), 69 and 7 mo for Rare recurring aberrations, and 59 and 7 mo for Unique (nonrecurring) balanced aberration (latency P ≤ 0.016 for all pairwise comparisons; OS, P ≤ 0.018 for all pairwise comparisons). The percentages of 21q22 patients surviving 1 year, 2 years, and 5 years were 58%, 33%, and 18%, respectively. Noticeable differences were observed in median OS between 21q22 patients (n = 7) receiving transplant (BMT) (31 mo) compared to 21q22 patients who received intensive non‐BMT therapy (n = 46) (17 mo); however, this was nonsignificant because of the small sample size (log‐rank, P = 0.33). t‐MDS/t‐AML with balanced 21q22 aberrations was associated with prior exposure to radiation, epipodophyllotoxins, and anthracyclines, dysplastic morphologic features, multiple partner chromosomes, and longer latency periods when compared to 11q23 and inv(16) t‐MDS/AML Workshop subgroups. In general, patients could be divided into two prognostic risk groups, those with t(8;21) (median OS, 19 mo) and those without t(8;21) (median OS, 7 mo) leukemia (log‐rank, P = 0.0007). © 2002 Wiley‐Liss, Inc.
Comprehensive mutational analysis of the VHL gene in sporadic renal cell carcinoma: Relationship to clinicopathological parameters
Authors: Kondo Keiichi , Yao Masahiro , Yoshida Minoru , Kishida Takeshi , Shuin Taro , Miura Takeshi , Moriyama Masatoshi , Kobayashi Kazuki , Sakai Naoki , Kaneko Shigeki , Kawakami Satoshi , Baba Masaya , Nakaigawa Noboru , Nagashima Yoji , Nakatani Yukio , Hosaka Masahiko 
Published: August 2002

AbstractTo delineate more precisely the somatic von Hippel‐Lindau disease (VHL) gene alteration as well as to elucidate its etiologic role in renal tumorigenesis, we examined a total of 240 sporadic renal cell carcinomas (RCCs) for somatic VHL gene alterations by DNA‐SSCP followed by sequencing, methylation‐specific PCR assay, microsatellite LOH study, and Southern blot analysis. Intragenic mutation of the VHL gene was found exclusively in clear‐cell or variant‐type RCCs at a frequency of 51% (104/202). Hypermethylation of the VHL promoter region was detected in an additional 11 clear‐cell RCCs. Microsatellite analysis demonstrated that LOH of the VHL locus was found in 140/155 (90%) informative clear‐cell RCCs. The VHL gene therefore seems to be inactivated in a two‐hit manner by intragenic mutation or hypermethylation plus allelic loss in clear‐cell RCC. Genomic rearrangement of the VHL gene detected by Southern analysis was not found (0/216 cases); this is in contrast to germ lines in which Southern aberrations consisted of 7–19% of the mutations. Clinicopathologic data demonstrated that VHL mutation/LOH did not vary according to tumor progression in clear‐cell RCC, including tumor diameter, stage, grading, distant metastasis, and lymph node metastasis. Interestingly, VHL mutation was significantly less frequent in RCCs occurring in younger (≦ 55 years) than that in older (≧ 56 years) patients. These data suggested that the inactivation of the VHL tumor‐suppressor gene is a specific genetic change in clear‐cell RCC, and that it may occur at an early or first step in the clear‐cell tumorigenic pathway rather than as a late event. © 2002 Wiley‐Liss, Inc.
Exclusion of SMAD4 mutation as an early genetic change in human pancreatic ductal tumorigenesis
Authors: Inoue Hiroko , Furukawa Toru , Sunamura Makoto , Takeda Kazunori , Matsuno Seiki , Horii Akira 
Published: August 2002

AbstractPancreatic ductal carcinoma is one of the malignant diseases with the poorest prognosis. To develop effective methods for better treatment of pancreatic cancer patients, we tried to analyze the course of multistep carcinogenesis of the pancreatic ductal cells. IPMT (intraductal papillary‐mucinous tumor) is thought to be one of the premalignant lesions of the pancreas, which would transform into carcinomas. Loss of 18q at the SMAD4 locus is known to be an early genetic change in pancreatic ductal carcinomas. It is not clear, however, whether or not the target gene for inactivation is SMAD4. Using 18 IPMTs, we analyzed LOH at the SMAD4 locus and observed frequent LOH (7/14, 50%). No mutations were observed in any of the tumors. Moreover, the expression level of the SMAD4 protein did not show a reduction in IPMTs. These results suggested that (i) inactivating mutation of the SMAD4 gene is a rather late genetic change in pancreatic carcinogenesis, and (ii) there may be an unknown tumor suppressor gene in 18q, other than SMAD4, that is involved in pancreatic ductal carcinogenesis. © 2001 Wiley‐Liss, Inc.
Identification of tumor metastasis suppressor region on the short arm of human chromosome 20
Authors: Goodarzi Goodarz , Mashimo Tomoyuki , Watabe Misako , Cuthbert Andrew P. , Newbold Robert F. , Pai Sudha K. , Hirota Shigeru , Hosobe Sadahiro , Miura Kunio , Bandyopadhyay Sucharita , Gross Steven C. , Balaji Kethandapatti C. , Watabe Kounosuke 
Published: August 2002

AbstractAcquisition of metastatic ability by prostate cancer cells is the hallmark of their lethal trait and outcome. However, the genetic alterations underlying the clinical progression and pathogenesis of prostate cancer are not well understood. Several studies involving loss of heterozygosity (LOH) and comparative genomic hybridization analysis have identified distinctively altered regions on various human chromosomes, and genomic imbalance of chromosome 20 was implicated in progression and recurrence of prostate tumors. To examine the role of chromosome 20 in prostate neoplasms, we introduced this chromosome into highly metastatic rat prostate cancer cells using the microcell‐mediated chromosome transfer technique. Introduction of the chromosome resulted in significant suppression of the metastatic ability of the hybrid cells, by as much as 98%, without any interference with the in vivo growth rate or tumorigenicity of primary tumor in SCID mice. Our STS‐PCR analysis on 10 hybrid clones indicates that the suppressor activity of chromosome 20 is located in the p11.23‐12 region. Further examination of the hybrid clones by experimental metastasis assay and histologic analysis as well as Matrigel invasion assay suggests the involvement of the suppressor region at an early stage of invasion and extravasation. We also investigated the status of the chromosome 20 suppressor region in pathology specimens from human prostate cancer patients and detected the frequent loss of this region in high‐grade tumors. These results suggest the presence of a putative suppressor gene on human chromosome 20 that is functionally involved in development of prostate cancer metastases. © 2001 Wiley‐Liss, Inc.
Microsatellite instability, mitochondrial DNA large deletions, and mitochondrial DNA mutations in gastric carcinoma
Authors: Máximo Valdemar , Soares Paula , Seruca Raquel , Rocha Ana Sofia , Castro Patrícia , Sobrinho‐Simões Manuel 
Published: August 2002

AbstractMitochondrial DNA (mtDNA) large deletions and mtDNA mutations have been demonstrated in various types of human cancer. The relationship between the occurrence of such alterations and the nuclear microsatellite instability (MSI) status of the neoplastic cells remains controversial. In an attempt to clarify the situation in gastric carcinoma, we studied, by PCR/SSCP and sequencing, five mitochondrial genes and two D‐loop regions in 32 gastric carcinomas that had been previously screened for MSI and mitochondrial common deletion. MtDNA alterations were detected in 26 carcinomas (81%). All the mtDNA mutations, which occurred mainly in the D‐loop and ND1 and ND5 genes, were transitions. D‐loop alterations (insertions and/or deletions) were not significantly associated with mutations in the coding regions. There was a trend towards an inverse relationship between the occurrence of mitochondrial common deletion and mtDNA mutations. No significant relationship was observed between MSI status and mtDNA mutations, whereas the mitochondrial common deletion appeared to be almost exclusively restricted to MSI‐negative tumors. The latter finding—almost no gastric carcinoma with MSI‐positive phenotype has large deletions of mtDNA—needs to be confirmed in a larger series and in tumors from other organs. © 2001 Wiley‐Liss, Inc.
Cre‐mediated transgene activation in the developing and adult mouse brain
Authors: Cinato Elisa , Mirotsou Maria , Sablitzky Fred 
Published: August 2002

AbstractSummary: The neuron‐specific rat enolase (NSE) promoter was employed to establish transgenic mice expressing Cre recombinase in the central nervous system. Founders were crossed with dormant lacZ indicator mice and specificity as well as efficiency of Cre‐mediated transgene activation was determined by PCR and/or X‐gal staining. Whereas most transgenic lines exhibited Cre activity in early development resulting in widespread Cre activity, one line (NSE‐Cre26) expressed high levels of Cre in the developing and adult brain. With the exception of kidney, which showed occasionally low level of Cre activity, Cre recombination in double transgenics was restricted to the nervous system. Whole‐mount X‐gal staining of 9.5 dpc embryos indicated Cre‐mediated lacZ expression in forebrain, hindbrain, and along the midbrain flexure. A similar expression pattern was observed during later stages of embryogenesis (11.5–13.5 dpc). In adult mice, Cre recombinase was expressed in cerebral cortex and cerebellum and high levels of Cre‐mediated lacZ expression were observed in hippocampus, cortex, and septum. The NSE‐Cre26 transgenic mouse line thus provides a useful tool to specifically overexpress and/or inactivate genes in the developing and adult brain. genesis 31:118–125, 2001. © 2001 Wiley‐Liss, Inc.
DNA methylation variation in cloned mice
Authors: Ohgane Jun , Wakayama Teruhiko , Kogo Yasushi , Senda Sho , Hattori Naka , Tanaka Satoshi , Yanagimachi Ryuzo , Shiota Kunio 
Published: August 2002

AbstractSummary: Mammalian cloning has been accomplished in several mammalian species by nuclear transfer. However, the production rate of cloned animals is quite low, and many cloned offspring die or show abnormal symptoms. A possible cause of the low success rate of cloning and abnormal symptoms in many cloned animals is the incomplete reestablishment of DNA methylation after nuclear transfer. We first analyzed tissue‐specific methylation patterns in the placenta, skin, and kidney of normal B6D2F1 mice. There were seven spots/CpG islands (0.5% of the total CpG islands detected) methylated differently in the three different tissues examined. In the placenta and skin of two cloned fetuses, a total of four CpG islands were aberrantly methylated or unmethylated. Interestingly, three of these four loci corresponded to the tissue‐specific loci in the normal control fetuses. The extent of aberrant methylation of genomic DNA varied between the cloned animals. In cloned animals, aberrant methylation occurred mainly at tissue‐specific methylated loci. Individual cloned animals have different methylation aberrations. In other words, cloned animals are by no means perfect copies of the original animals as far as the methylation status of genomic DNA is concerned. genesis 30:45–50, 2001. © 2001 Wiley‐Liss, Inc.
Cloning and sequence analysis of a zebrafish cDNA encoding DNA (cytosine‐5)‐methyltransferase‐1
Authors: Mhanni Aizeddin A. , Yoder Jeffrey A. , Dubesky Christa , McGowan Ross A. 
Published: August 2002

AbstractSummary: The zebrafish has become a well‐established animal model for the analysis of development and of several disease phenotypes. Several of the favorable traits that make it a popular model organism would also be beneficial for the study of normal and abnormal vertebrate development in which DNA methylation may play a role. We report the determination of the full‐length cDNA sequence corresponding to the zebrafish DNA (cytosine‐5‐) methyltransferase gene, Dnmt1. It is 4,907 bases long and has an open reading frame predicted to encode a 1,499 amino acid protein that is similar in size and sequence to a number of other methyltransferases identified in other organisms. genesis 30:213–219, 2001. © 2001 Wiley‐Liss, Inc.
Interactions between genetic and reproductive factors in breast cancer risk in a population‐based sample of African‐American families
Authors: Chaudru Valérie , Laing Amelia , Dunston Georgia M. , Adams‐Campbell Lucile L. , Williams Rosemary , Lynch John J. , Leffall Lasalle D. , Dewitty Robert L. , Gause Barry L. , Bonney George E. , Demenais Florence 
Published: August 2002

AbstractIncidence of breast cancer (BC) varies among ethnic groups, with higher rates in white than in African‐American women. Until now, most epidemiological and genetic studies have been carried out in white women. To investigate whether interactions between genetic and reproductive risk factors may explain part of the ethnic disparity in BC incidence, a genetic epidemiology study was conducted, between 1989 and 1994, at the Howard University Cancer Center (Washington, DC), which led to the recruitment of 245 African‐American families. Segregation analysis of BC was performed by use of the class D regressive logistic model that allows for censored data to account for a variable age of onset of disease, as implemented in the REGRESS program. Segregation analysis of BC was consistent with a putative dominant gene effect (P < 0.000001) and residual sister‐dependence (P < 0.0001). This putative gene was found to interact significantly with age at menarche (P = 0.048), and an interaction with a history of spontaneous abortions was suggested (P = 0.08). A late age at menarche increased BC risk in gene carriers but had a protective effect in non‐gene carriers. A history of spontaneous abortions had a protective effect in gene carriers and increased BC risk in non‐gene carriers. Our findings agree partially with a similar analysis of French families showing a significant gene × parity interaction and a suggestive gene × age at menarche interaction. Investigating gene × risk factor interactions in different populations may have important implications for further biological investigations and for BC risk assessment. Genet. Epidemiol. 22:285–297, 2002. © 2002 Wiley‐Liss, Inc.
Power and robustness of a score test for linkage analysis of quantitative traits using identity by descent data on sib pairs
Authors: Goldstein Darlene R. , Dudoit Sandrine , Speed Terence P. 
Published: August 2002

AbstractIdentification of genes involved in complex traits by traditional (lod score) linkage analysis is difficult due to many complicating factors. An unfortunate drawback of non‐parametric procedures in general, though, is their low power to detect genetic effects. Recently, Dudoit and Speed [2000] proposed using a (likelihood‐based) score test for detecting linkage with IBD data on sib pairs. This method uses the likelihood for θ, the recombination fraction between a trait locus and a marker locus, conditional on the phenotypes of the two sibs to test the null hypothesis of no linkage (θ = ½). Although a genetic model must be specified, the approach offers several advantages. This paper presents results of simulation studies characterizing the power and robustness properties of this score test for linkage, and compares the power of the test to the Haseman‐Elston and modified Haseman‐Elston tests. The score test is seen to have impressively high power across a broad range of true and assumed models, particularly under multiple ascertainment. Assuming an additive model with a moderate allele frequency, in the range of p = 0.2 to 0.5, along with heritability H = 0.3 and a moderate residual correlation ρ = 0.2 resulted in a very good overall performance across a wide range of trait‐generating models. Generally, our results indicate that this score test for linkage offers a high degree of protection against wrong assumptions due to its strong robustness when used with the recommended additive model. Genet. Epidemiol. 20:415–431, 2001. © 2001 Wiley‐Liss, Inc.
Evidence for further breast cancer susceptibility genes in addition to BRCA1 and BRCA2 in a population‐based study
Authors: Antoniou Antonis C. , Pharoah Paul D.P. , McMullan Greg , Day Nickolas E. , Ponder Bruce A.J. , Easton Douglas 
Published: August 2002

AbstractWe used data from a population based series of breast cancer patients to investigate the genetic models that can best explain familial breast cancer not due to the BRCA1 and BRCA2 genes. The data set consisted of 1,484 women diagnosed with breast cancer under age 55 registered in the East Anglia Cancer registry between 1991–1996. Blood samples taken from the patients were analysed for mutations in BRCA1 and BRCA2. The genetic models were constructed using information on breast and ovarian cancer history in first‐degree relatives and on the mutation status of the index patients. We estimated the simultaneous effects of BRCA1, BRCA2, a third hypothetical gene BRCA3, and a polygenic effect. The models were assessed by likelihood comparisons and by comparison of the observed numbers of mutations and affected relatives with the predicted numbers. BRCA1 and BRCA2 could not explain all the familial clustering of breast cancer. The best‐fitting single gene model for BRCA3 was a recessive model with a disease allele frequency 24% and penetrance 42% by age 70. However, a polygenic model gave a similarly good fit. The estimated population frequencies for BRCA1 and BRCA2 mutations were similar under both recessive and polygenic models, 0.024 and 0.041%, respectively. A dominant model for BRCA3 gave a somewhat worse fit, although the difference was not significant. The mixed recessive model was identical to the recessive model and the mixed dominant very similar to the polygenic model. The BRCA3 genetic models were robust to the BRCA1 and BRCA2 penetrance assumptions. The overall fit of all models was improved when the known effects of parity on breast and ovarian cancer risks were included in the model—in this case a polygenic model fits best. These findings suggest that a number of common, low‐penetrance genes with additive effects may account for the residual non‐BRCA1/2 familial aggregation of breast cancer, but Mendelian inheritance of an autosomal recessive allele cannot be ruled out. Genet. Epidemiol. 21:1–18, 2001. © 2001 Wiley‐Liss, Inc.
Efficiency of DNA pooling to estimate joint allele frequencies and measure linkage disequilibrium
Authors: Pfeiffer Ruth M. , Rutter Joni L. , Gail Mitchell H. , Struewing Jeffery , Gastwirth Joseph L. 
Published: August 2002

AbstractPooling DNA samples can yield efficient estimates of the prevalence of genetic variants. We extend methods of analyzing pooled DNA samples to estimate the joint prevalence of variants at two or more loci. If one has a sample from the general population, one can adapt the method for joint prevalence estimation to estimate allele frequencies and D, the measure of linkage disequilibrium. The parameter D is fundamental in population genetics and in determining the power of association studies. In addition, joint allelic prevalences can be used in case‐control studies to estimate the relative risks of disease from joint exposures to the genetic variants. Our methods allow for imperfect assay sensitivity and specificity. The expected savings in numbers of assays required when pooling is utilized compared to individual testing are quantified. Genet. Epidemiol. 22:94–102, 2002. © 2002 Wiley‐Liss, Inc.
Modifications of retinal afferent activity induce changes in astroglial plasticity in the hamster circadian clock
Authors: Lavialle Monique , Begue Anne , Papillon Catherine , Vilaplana Jordi 
Published: August 2002

AbstractThe circadian clock, located in the suprachiasmatic nucleus (SCN) of the hypothalamus in mammals, exhibits astroglial plasticity indicated by GFAP expression over the 24‐h period. In this study, we evaluated the role of neuronal retinal input in the observed changes. Modifications of retinal input, either by rearing animals under darkness (DD) or under constant light (LL), or by suppressing afferent input (bilateral enucleation), induced drastic changes in astroglial plasticity. In enucleated animals, a dramatic decrease in GFAP expression was evident in the area of the SCN deprived of retinal projections, whereas persistence of a rhythmic variation was in those areas still exhibiting GFAP expression. By contrast, no changes in astrocytic plasticity were detected in hamsters maintained under LL. These data suggest two fundamental roles for astrocytes within the SCN: (1) to regulate and mediate glutamate released by retinal terminals throughout the neuronal network to facilitate photic signal transmission; (2) to contribute to synchronization between suprachiasmatic neurons. GLIA 34:88–100, 2001. © 2001 Wiley‐Liss, Inc.