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G Samara

Publications and source records attributed to G Samara.

11 recordsLinked to original sources
PubMed1999

Physical map of the region surrounding the ataxia-telangiectasia gene on human chromosome 11q22-23.

Ataxia telangiectasia (A-T) is an autosomal recessive disease affecting multiple systems, including the development of the cerebellum and thymus. This results in a progressive cerebellar ataxia with onset between 1-3 years, telangiectasia occurs within the subsequent 3-5 years. We localized the A-T gene by linkage analysis to chromosome 11q22-23, between the markers D11S384, and D11S535, and constructed a series of contigs using three BACs and twelve cosmids, spanning a region of approximately 400 kb. We developed a set of sequence-tagged site (STS) markers from the ends of the BACs and cosmids. The A-T gene was isolated from within this region. It is now possible to precisely orient specific BACs, cosmids, and STSs with respect to the exons of the A-T gene (ATM). We anticipate that this information will be useful for further studies of functional domains and regulatory elements within the ATM gene, as well as for other genes in this region. In addition, these clones can be used for FISH studies of deletions, translocations and for loss of heterozygosity in various tumors.

Ataxia Telangiectasia↗
PubMed1999

Identification of a 5-cM region of common allelic loss on 8p12-p21 in human breast cancer and genomic analysis of the hEXT1L/EXTR1/EXTL3 gene in this locus.

The short arm of chromosome 8 is frequently lost in many human carcinomas including breast cancer, suggesting the presence of a tumor suppressor gene(s) in this region. We identified a gene termed hEXT1L/EXTR1/EXTL3 (hEXT1L hereinafter) that was mapped to chromosome bands 8p12-p21 where frequent LOHs of this region was reported in breast cancer. The existence of the third breast cancer susceptibility gene was also suggested in this region by linkage analysis. We further performed LOH analysis in 8p12-p21 in 34 breast cancers and identified a 5-cM region of common allelic loss that overlapped with the locus for positive lod score in familial breast cancer. We further analyzed genomic alterations of hEXT1L in tumors in which frequent LOHs of 8p were reported. A total of 327 cancers (313 primary tumors and 14 cancer cell lines) including 22 primary breast cancers were analyzed, but none of the tumors had somatic mutations: only one thyroid cancer patient without any family history of cancer had a 9-bp insertion in the constitutional DNA. These results suggest that mutations of hEXT1L do not play a major role in the development of sporadic cancers including breast cancer, and that other tumor suppressor gene(s) exists in the 5-cM region identified in this study.

Alleles↗
PubMed1998

Mutational analysis of the PTEN gene in head and neck squamous cell carcinoma.

Loss of heterozygosity (LOH) at chromosome band 10q23 occurs frequently in a wide variety of human tumors. A recently identified candidate tumor suppressor gene, PTEN located on 10q23, is mutated in multiple advanced cancers. To explore whether PTEN is associated with human squamous cell carcinoma of the head and neck (SCCHN), DNAs from both normal muscle and tumor tissue in 19 SCCHN were used for detecting LOH at chromosome 10q23 and mutational analysis of PTEN by direct polymerase chain reaction (PCR)-DNA sequencing. LOH at 10q23 was identified in 6/15 SCCHN. Mutation of PTEN was identified in 3/19 SCCHN. Of these 3 patients, 2 had stage IV disease; the third patient, with recurrent, metastatic and stage III disease, showed a 36 bp germline heterozygous deletion within intron 7. Furthermore, a missense mutation at codon 501 (TCT --> TTT: Ser --> Phe) in exon 8 was also found in tumor from the same patient. Our results suggest that PTEN may play a role in the genesis of some SCCHNs.

Amino Acid Substitution↗
PubMed1997

A transcript map encompassing the multiple endocrine neoplasia type-1 (MEN1) locus on chromosome 11q13.

A transcription map of a 1200-kb region encompassing the MEN1 locus was constructed by direct cDNA selection and mapping ESTs. A total of 29 genes were mapped. Ten transcripts were identified by cDNA selection of a focused 300-kb genomic region telomeric to the MEN1 consensus region. Since many of the sequences cloned by cDNA selection also identified ESTs from the region, 19 additional RH-mapped ESTs were mapped to the entire contig region by PCR amplification of genomic clones. Nine known genes, 2 putative human homologues to mouse genes, and 18 novel transcripts map to the region. Transcripts that map to the MEN1 interval PYGM-D11S449 include SGC35223, IB1256, AA147620, ZFM1, FAU, and CAPN1. The latter 3 known genes have already been excluded as candidate MEN1 genes. The 2 putative human homologues of mouse genes Ltbp2 and Spa-1 may be candidate tumor suppressor genes, but they map telomeric to D11S449. Although both of these genes map outside the MEN1 consensus region they may play a role in sporadic endocrine tumors independent of the MEN1 gene or in other tumors, such as breast cancer, that have loss of heterozygosity within this region.

Blotting, Northern↗
PubMed1995

A novel L23-related gene 40 kb downstream of the imprinted H19 gene is biallelically expressed in mid-fetal and adult human tissues.

The closely linked IGF2 and H19 genes on human chromosome 11p15.5 are monoallelically expressed as a result of genomic imprinting and show altered expression in Wilms' tumors (WTs). To map regional imprinting we have sought to isolate additional human genes close to IGF2/H19 and to characterize their allelic expression patterns. Here we report a novel gene, provisionally named L23MRP [L23 (mitochondrial)-related protein], which is oriented 'tail-to-tail' with H19 and is transcribed to within 40 kb of the last H19 exon. L23MRP is expressed biallelically in many mid-fetal and adult human tissues. This gene is also expressed at normal levels in WTs which have lost expression of H19 either via loss of the maternal chromosome 11p15.5 or via an epigenetic pathway involving site-specific DNA hypermethylation. These data indicate that, at least in post-embryonic stages, L23MRP is functionally insulated from the IGF2/H19 imprinted domain.

Adult↗
PubMed1995

MTS1/p16/CDKN2 lesions in primary glioblastoma multiforme.

The multiple tumor suppressor 1 (MTS1) gene encoding the p16 inhibitor of cyclin-dependent kinase 4 is deleted or mutated in a wide variety of human tumor cell lines, but the importance of this gene as a tumor suppressor in vivo appears to be highly dependent on tumor type. Because MTS1/p16/CDKN2 and the homologous MTS2/p15 gene map to a region of chromosome 9p21, which is frequently deleted in malignant gliomas, we searched for lesions of these genes in primary biopsies of glioblastoma multiforme (GBM). Our analysis confirms a sizable frequency of homozygous deletion of MTS1/p16/CDKN2 (9/27 cases) and also reveals a low but detectable frequency of intragenic DNA lesions (one point mutation in exon 2 leading to premature termination) among GBMs that retain one or both copies of the gene. No mutations were found in exon 2 of MTS2/p15 (12 cases examined), and one GBM showed a DNA deletion breakpoint in the 30 kb between MTS1/p16/CDKN2 and MTS2/p15 resulting in deletion of MTS1/p16/CDKN2 with retention of MTS2/p15. In contrast to the high-grade tumors, none of 12 low-grade gliomas showed MTS1/p16/CDKN2 deletions. These data support a role for MTS1/p16/CDKN2 as a tumor suppressor gene in the in vivo evolution of GBMs. Given that two tumors with hemizygous MTS1/p16/CDKN2 deletions and loss of heterozygosity for chromosome 9p21 did not contain detectable intragenic mutations, there may be one or more additional relevant 9p21 tumor suppressor genes.

Base Sequence↗
PubMed1993

Human Genome Project.

The Human Genome Project is an international effort to clone and sequence the entire human genome. This audacious undertaking, estimated to cost 200 million dollars per year and require 15 years to complete, promises to be one of the most revolutionary and captivating scientific endeavors ever conceived by mankind. By knowing the sequence of the estimated 3 billion base pairs of the haploid human genome and its more than 30,000 genes, many questions will be answered. Moreover, our ability to intervene at the genetic level will be possible. This review outlines the scientific goals and methods of this project and discusses some of its ethical, legal, and social ramifications.

Base Sequence↗
PubMed1993

Molecular biology and therapy of disease.

Molecular biology will have a profound impact upon the treatment of disease. Molecular techniques provide protein products for treatment of more diseases each year. The understanding of pathophysiology at the molecular level allows for improved drug design. Antisense technology can selectively control gene expression. Gene therapy is potentially the most important aspect of molecular biology. Physical and viral transduction mechanisms are being developed toward this end. Gene replacement, creation of antisense oligonucleotides, and prodrug strategies are being developed. Currently, gene replacement and prodrug therapy are feasible in at least a few cases, but further study will yield additional applications.

Antisense Elements (Genetics)↗
PubMed1992

Molecular biology: an overview.

An overview of molecular biology is presented for the practicing surgeon. Definitions of the constructs and activity of DNA, RNA, and protein synthesis are defined. These principles are illustrated in their use in recombinant DNA technologies. A glossary is provided for the terms utilized.

DNA, Recombinant↗
PubMed1992

Molecular mechanisms of tumor formation.

DNA is the fundamental guide for the cell's processes. The alterations in DNA that can lead to abnormal or absent proteins and the role of chromosomal alterations in changing the function of the DNA are reviewed. The role of viruses in derailing a cell's normal functions, the major mechanisms of oncogene action, and tumor suppressor genes are also discussed.

DNA, Neoplasm↗