The Experts below are selected from a list of 246 Experts worldwide ranked by ideXlab platform
Adi F Gazdar - One of the best experts on this subject based on the ideXlab platform.
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Deletions of Chromosome 4 occur early during the pathogenesis of colorectal carcinoma
Human Pathology, 2001Co-Authors: Narayan Shivapurkar, Anirban Maitra, Sara Milchgrub, Adi F GazdarAbstract:Abstract Allelic losses at one or both arms of Chromosome 4 are frequent in several tumor types, but information about colorectal carcinoma is limited. We have previously defined 4 nonoverlapping regions of frequent deletions in several tumor types. In an effort to more precisely locate the putative tumor suppressor gene(s) on Chromosome 4 involved in the multistage pathogenesis of colorectal carcinomas, we performed loss of heterozygosity (LOH) studies using 19 polymorphic microsatellite markers. After precise microdissection of archival surgical cases, we determined LOH in DNA obtained from 23 colorectal adenocarcinomas, 20 colorectal adenomas, and from corresponding histologically normal-appearing colonic epithelial samples adjacent to the tumors and at the resection margins. We observed localized deletions of Chromosome 4 at multiple regions in both carcinomas and adenomas. We identified deletions at 4 previously identified regions: R1 at 4q33-34 (18%-33%), R2 at 4q25-26 (45%-65%), R3 at 4p15.1-15.3 (35%-47%), and R4 at 4p16.3 (40%-49%). Six of fifteen (40%) cases examined with deletions of Chromosome 4 in either adenocarcinomas or adenomas had loss of the same parental alleles in adjacent histologically normal epithelium but not in epithelial samples from the surgical resection margins. The deletions, which commenced on the short arm of Chromosome 4 (regions R3 and/or R4), were more extensive in adenocarcinomas, intermediate in length in adenomas, and least extensive in histologically normal epithelium. Our results suggest that there may be multiple putative tumor suppressor genes located on both arms of Chromosome 4 whose inactivation are important early events in the pathogenesis of colorectal carcinoma. H UM P ATHOL 32:169-177. Copyright © 2001 by W.B. Saunders Company
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multiple regions of Chromosome 4 demonstrating allelic losses in breast carcinomas
Cancer Research, 1999Co-Authors: Narayan Shivapurkar, Sanjay Sood, Ignacio I Wistuba, Arvind K Virmani, Anirban Maitra, Sara Milchgrub, John D Minna, Adi F GazdarAbstract:Allelotyping studies suggest that allelic losses at one or both arms of Chromosome 4 are frequent in several tumor types, but information about breast cancer is scant. A recent comparative genomic hybridization analysis revealed frequent losses of Chromosome 4 in breast carcinomas. In an effort to more precisely locate the putative tumor suppressor gene(s) on Chromosome 4 involved in the pathogenesis of breast carcinomas, we performed loss of heterozygosity studies using 19 polymorphic microsatellite markers. After precise microdissection of archival surgical cases, we analyzed DNA obtained from 44 breast carcinomas for loss of heterozygosity. In addition, DNA from tumor cell lines derived from 14 of these 44 breast carcinomas were also analyzed. We observed deletions of Chromosome 4 at multiple sites in both tumor cell lines and breast carcinomas. The deletions in cell lines and their corresponding tumors were extensive in nature, whereas they were more localized in noncultured breast carcinomas. The localized deletions in the noncultured breast carcinomas clearly defined four nonoverlapping regions of frequent deletions: 4q33–34 (76%); 4q25–26 (63%); 4p15.1–15.3 (57%); and 4p16.3 (50%). Our results suggest that there may be multiple putative tumor suppressor genes, located on both arms of Chromosome 4, whose inactivation is important in the pathogenesis of breast cancer.
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deletions of Chromosome 4 at multiple sites are frequent in malignant mesothelioma and small cell lung carcinoma
Clinical Cancer Research, 1999Co-Authors: Narayan Shivapurkar, Ignacio I Wistuba, Arvind K Virmani, Sara Milchgrub, John D Minna, Adi F Gazdar, Bruce MackayAbstract:Recent allelotyping studies suggest that allelic losses at one or both arms of Chromosome 4 are frequent in several tumor types. Cytogenetic studies of malignant mesothelioma (MM) and comparative genomic hybridization analyses of small cell lung carcinoma (SCLC) suggest that Chromosome 4 deletions may also play a role in these tumor types, although these results have not been confirmed by allelotyping. In an effort to more precisely identify and map the locations of putative tumor suppressor gene(s) on Chromosome 4 involved in the pathogenesis of these tumors, we performed loss of heterozygosity studies using 16 polymorphic microsatellite markers. After precise microdissection of archival surgical cases, we studied DNA obtained from 20 MMs, 21 SCLCs, and 20 non-SCLCs (NSCLCs). In addition, DNA from 14 SCLC and 17 NSCLC cell lines and corresponding B lymphoblastoid lines were studied. In MM and SCLC, we observed frequent losses at three nonoverlapping regions: ( a ) 4q33–34 (region R1; >80%); ( b ) 4q25–26 (region R2; >60%); and ( c ) 4p15.1–15.3 (region R3; >50%). Losses at these sites occurred at lower frequencies in NSCLC (>20–30%). Data from tumors and cell lines were similar. In MM and SCLC, the most frequently observed pattern was loss at all three regions. However, in NSCLC, the most frequent pattern was loss at R3 alone. Our study has delineated three nonoverlapping regions of frequent deletions on Chromosome 4 in MM and SCLC, suggesting that there may be three putative suppressor genes on Chromosome 4, the inactivation of which may be important in the pathogenesis of these tumor types.
Frank Greenberg - One of the best experts on this subject based on the ideXlab platform.
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molecular confirmation of wolf hirschhorn syndrome with a subtle translocation of Chromosome 4
American Journal of Human Genetics, 1991Co-Authors: Michael R. Altherr, John J. Wasmuth, James F. Gusella, Ulla Bengtsson, F F B Elder, David H Ledbetter, M E Mcdonald, Frank GreenbergAbstract:Wolf-Hirschhorn syndrome is a clinically recognizable, multiple congenital anomaly syndrome usually associated with terminal deletion of the short arm of Chromosome 4. A girl with clinical features of Wolf-Hirschhorn syndrome did not show an obvious deletion of Chromosome 4, and a molecular defect was suspected. RFLPs of genomic DNA from the proband and her parents were studied using DNA probes from the distal region of Chromosome 4p. Fluorescence in situ hybridization using a cosmid p847.351 containing the fragment 847 E-C was performed to investigate the possibility of a subtle translocation. Cytogenetic analyses done on the child and on both parents did not conclusively reveal abnormalities of Chromosome 4. Molecular studies using two probes mapped to distal 4p showed the absence of the maternal haplotype in the child. These findings are thus consistent with a molecular deletion of 4p and confirm the diagnosis of Wolf-Hirschhorn syndrome. Cytogenetic experiments involving fluorescence in situ hybridization showed that the mother carried a subtle translocation between Chromosomes 4 and 19, 46,XX,t(4,19)(p16.3; p13.3), which resulted in an unbalanced form in the child. Chorionic villus sampling for prenatal diagnosis in a subsequent pregnancy showed the fetus to be unaffected. This provides the first evidence, in Chromosome 4p, of a molecular deletion due to a subtle, inherited translocation leading to the Wolf-Hirschhorn phenotype. Such subtle translocations may become an important mechanism for some recurrent genetic defects.
Peter A Steck - One of the best experts on this subject based on the ideXlab platform.
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deletion mapping of Chromosome 4 in head and neck squamous cell carcinoma
Oncogene, 1997Co-Authors: Mark A Pershouse, Adel K Elnaggar, Kenneth Hurr, W Alfred K Yung, Peter A SteckAbstract:: Genomic deletions involving Chromosome 4 have recently been implicated in several human cancers. To identify and characterize genetic events associated with the development of head and neck squamous cell carcinoma (HNSCC), a fine mapping of allelic losses associated with Chromosome 4 was performed on DNA isolated from 27 matched primary tumor specimens and normal tissues. Loss of heterozygosity (LOH) of at least one Chromosome 4 polymorphic allele was seen in the majority of tumors (92%). Allelic deletions were confined to short arm loci in four tumors and to the long arm loci in 12 tumors, suggesting the presence of two regions of common deletion. One region of frequent deletion was centered at D4S405 on 4p and included the loci D4S1546 to D4S428 in approximately 41% of the tumors. The common region of deletion on 4q was more complex and extended from D4S1571 to D4S1573. Frequent genetic alterations were observed within this region (4q25) and one marker, D4S407, exhibited a high frequency of LOH (>75%). These results indicate that alterations of Chromosome 4 regions are associated with HNSCC tumorigenesis and further localizes the regions that may harbor tumor suppressor genes.
Qi Feng - One of the best experts on this subject based on the ideXlab platform.
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structural features of the rice Chromosome 4 centromere
Nucleic Acids Research, 2004Co-Authors: Yu Zhang, Qi Feng, Ying Li, Qiang Zhao, Yuchen Huang, Lei Zhang, Tingting Lu, Yiqi Lu, Zhukuan Cheng, Rod A WingAbstract:A complete sequence of a Chromosome centromere is necessary for fully understanding centromere function. We reported the sequence structures of the first complete rice Chromosome centromere through sequencing a large insert bacterial artificial Chromosome clone-based contig, which covered the rice Chromosome 4 centromere. Complete sequencing of the 124-kb rice Chromosome 4 centromere revealed that it consisted of 18 tracts of 379 tandemly arrayed repeats known as CentO and a total of 19 centromeric retroelements (CRs) but no unique sequences were detected. Four tracts, composed of 65 CentO repeats, were located in the opposite orientation, and 18 CentO tracts were flanked by 19 retroelements. The CRs were classified into four types, and the type I retroelements appeared to be more specific to rice centromeres. The preferential insert of the CRs among CentO repeats indicated that the centromere-specific retroelements may contribute to centromere expansion during evolution. The presence of three intact retrotransposons in the centromere suggests that they may be responsible for functional centromere initiation through a transcription-mediated mechanism.
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sequence and analysis of rice Chromosome 4
Nature, 2002Co-Authors: Qi Feng, Yujun Zhang, Shengyue Wang, Gang Fu, Yucheng Huang, Ying Li, Xin Hu, Yu Zhang, Qiang Zhao, Kai YingAbstract:Rice is the principal food for over half of the population of the world. With its genome size of 430 megabase pairs (Mb), the cultivated rice species Oryza sativa is a model plant for genome research. Here we report the sequence analysis of Chromosome 4 of O. sativa, one of the first two rice Chromosomes to be sequenced completely. The finished sequence spans 34.6 Mb and represents 97.3% of the Chromosome. In addition, we report the longest known sequence for a plant centromere, a completely sequenced contig of 1.16 Mb corresponding to the centromeric region of Chromosome 4. We predict 4,658 protein coding genes and 70 transfer RNA genes. A total of 1,681 predicted genes match available unique rice expressed sequence tags. Transposable elements have a pronounced bias towards the euchromatic regions, indicating a close correlation of their distributions to genes along the Chromosome. Comparative genome analysis between cultivated rice subspecies shows that there is an overall syntenic relationship between the Chromosomes and divergence at the level of single-nucleotide polymorphisms and insertions and deletions. By contrast, there is little conservation in gene order between rice and Arabidopsis.
Yu Zhang - One of the best experts on this subject based on the ideXlab platform.
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structural features of the rice Chromosome 4 centromere
Nucleic Acids Research, 2004Co-Authors: Yu Zhang, Qi Feng, Ying Li, Qiang Zhao, Yuchen Huang, Lei Zhang, Tingting Lu, Yiqi Lu, Zhukuan Cheng, Rod A WingAbstract:A complete sequence of a Chromosome centromere is necessary for fully understanding centromere function. We reported the sequence structures of the first complete rice Chromosome centromere through sequencing a large insert bacterial artificial Chromosome clone-based contig, which covered the rice Chromosome 4 centromere. Complete sequencing of the 124-kb rice Chromosome 4 centromere revealed that it consisted of 18 tracts of 379 tandemly arrayed repeats known as CentO and a total of 19 centromeric retroelements (CRs) but no unique sequences were detected. Four tracts, composed of 65 CentO repeats, were located in the opposite orientation, and 18 CentO tracts were flanked by 19 retroelements. The CRs were classified into four types, and the type I retroelements appeared to be more specific to rice centromeres. The preferential insert of the CRs among CentO repeats indicated that the centromere-specific retroelements may contribute to centromere expansion during evolution. The presence of three intact retrotransposons in the centromere suggests that they may be responsible for functional centromere initiation through a transcription-mediated mechanism.
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sequence and analysis of rice Chromosome 4
Nature, 2002Co-Authors: Qi Feng, Yujun Zhang, Shengyue Wang, Gang Fu, Yucheng Huang, Ying Li, Xin Hu, Yu Zhang, Qiang Zhao, Kai YingAbstract:Rice is the principal food for over half of the population of the world. With its genome size of 430 megabase pairs (Mb), the cultivated rice species Oryza sativa is a model plant for genome research. Here we report the sequence analysis of Chromosome 4 of O. sativa, one of the first two rice Chromosomes to be sequenced completely. The finished sequence spans 34.6 Mb and represents 97.3% of the Chromosome. In addition, we report the longest known sequence for a plant centromere, a completely sequenced contig of 1.16 Mb corresponding to the centromeric region of Chromosome 4. We predict 4,658 protein coding genes and 70 transfer RNA genes. A total of 1,681 predicted genes match available unique rice expressed sequence tags. Transposable elements have a pronounced bias towards the euchromatic regions, indicating a close correlation of their distributions to genes along the Chromosome. Comparative genome analysis between cultivated rice subspecies shows that there is an overall syntenic relationship between the Chromosomes and divergence at the level of single-nucleotide polymorphisms and insertions and deletions. By contrast, there is little conservation in gene order between rice and Arabidopsis.