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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The chromosomal assignments of the two genes encoding the murine p53 cellular tumor antigen were determined by using a panel of mouse-Chinese hamster somatic cell hybrid clones and a mouse p53-specific cDNA clone. One gene, probably the functional member of the family, was found to be on chromosome 11. The other gene, which is probably a processed pseudogene, was assigned to chromosome 14. The potential relevance of these findings to documented cases of chromosome 11 trisomy are also discussed.
Mol Cell Biol 1984 Aug
PMID:The gene and the pseudogene for mouse p53 cellular tumor antigen are located on different chromosomes. 638 44

By analysis of skin tumors from F1 hybrid mice we demonstrated that the genetic events that occur during tumor progression depend on the type of chemical carcinogenesis protocol used to induce tumor growth. More than 95% of tumors induced by initiation with 7,12-dimethylbenz[a]anthracene (DMBA) and promotion with 12-O-tetradecanoyl-phorbol-13-acetate (TPA) exhibited mutations in Ha-ras and trisomy of chromosome 7. Carcinomas induced with multiple DMBA treatments had a lower frequency of alterations on chromosome 7 (50%), but only in tumors with Ha-ras mutations, and had a much wider spectrum of alterations, including trisomy, mitotic recombination, deletion, and gene duplication. Carcinomas induced with multiple N-methyl-N'-nitro-N-nitrosoguanidine treatments only rarely exhibited alterations on chromosome 7 (8%), even if they contained mutant Ha-ras. More frequent numerical alterations of chromosome 11 were also seen in TPA-promoted tumors (23%) than in tumors induced by multiple carcinogen treatments (8%). These results show that postinitiation events are nonrandom and fit a model in which promoting agents induce numerical chromosomal alterations but in which mutagens cause more directed mutational events.
Mol Carcinog 1994 Oct
PMID:Induction of different genetic changes by different classes of chemical carcinogens during progression of mouse skin tumors. 791 97

In order to investigate whether specific, nonrandom chromosome rearrangements were involved in the induction of hydroxyurea (HU) resistance in mouse SEWA cells, we undertook detailed cytogenetic analyses of three independently selected lines during the long-term treatment with HU. We found that cells with trisomy 12 had selective advantage during early steps of HU treatment. Subsequently, numerous rearrangements of chromosome 12 took place in each of the HU-resistant cell lines. More specifically, the proximal end of chromosome 12 (band A3) was frequently involved in breaks and fusions generating multicentric marker chromosomes. In situ hybridization showed that the functional Rrm2 gene was located in this particular region of chromosome 12. Furthermore, amplification and rearrangements of the structural gene Rrm2 were detected both at the chromosomal and at the molecular level. As discussed, the results of the cytogenetic analyses support the chromosomal breakage model of gene amplification.
Somat Cell Mol Genet 1994 Jul
PMID:Drug-specific rearrangements of chromosome 12 in hydroxyurea-resistant mouse SEWA cells: support for chromosomal breakage model of gene amplification. 797 3

As many as 16% of all recognized pregnancies may be anembryonic, with failure of the embryo at a very early stage of development leaving only the extraembryonic components of the conceptus to proliferate. Studies in the mouse have shown that the maternal and paternal contributions to the genome of the zygote are not functionally equivalent, due to parental genomic imprinting. Uniparental disomy can reveal imprinting effects, as in this phenomenon both members of a chromosome pair are inherited from the same parent. We have carried out a systematic search for uniparental disomy in tissues from 23 cases of early embryonic failure, using variable number tandem repeat (VNTR) analysis and PCR amplification of polymorphic short sequence repeats. Two cases of maternal uniparental heterodisomy for chromosome 21 were identified. One case occurred in conjunction with trisomy for chromosomes 7 and 9, but in the other case maternal uniparental heterodisomy for chromosome 21 was the only chromosomal abnormality found. We therefore postulate that there may be developmentally important genes on human chromosome 21 which are imprinted such that both parental copies are essential for normal embryogenesis.
Hum Mol Genet 1994 Aug
PMID:Early embryonic failure associated with uniparental disomy for human chromosome 21. 798 17

Neuropeptide Y (NPY)-containing neurons are depleted in the cortices of individuals with Alzheimer disease (AD), yet spared in the striatum of patients with Huntington chorea. It is unknown whether this neuronal phenotype is inherently susceptible to the neurodegenerative processes that are a hallmark of AD. To study this question, the murine trisomy 16 model of Down syndrome and Alzheimer disease was investigated. Since trisomic fetuses die in utero, studies were carried out on primary cultures of dissociated cortical neurons. These were prepared from 15-d gestational trisomy 16 fetuses and their littermate euploid controls, and examined by immunocytochemical staining for neuropeptide Y at 7 and 12 d in vitro. Trisomy 16 neurons were also grown on euploid glial carpets, whereas euploid neurons were grown on trisomic glia. The results demonstrate a significant increase in the number of NPY neurons and a stunting in the dendritic arbor of these neurons in trisomic vs euploid cortex. Both of these parameters could be normalized by direct contact with euploid glia. When euploid cortex was plated on trisomic glia, the number of NPY neurons and their morphology were altered so that they began to resemble trisomic NPY cortical neurons. These results indicate a dysregulation of NPY neuronal expression and differentiation in trisomy 16 cortex that are modifiable by interaction with euploid glia and imply an abnormal trophic (glial) environment in trisomic cortex.
Mol Chem Neuropathol 1994 Aug
PMID:Neuropeptide Y immunoreactive neurons in murine trisomy 16 cortical cultures. Plasticity of expression and differentiation. 799 28

TG.AC mice (which carry a v-Ha-ras transgene) rapidly develop papillomas in response to 12-O-tetradecanoylphorbol-13-acetate (TPA). Approximately 30% of the papillomas are associated with subsequent development of malignancies. Early-passage spindle-shaped tumor cells arising from explant cultures of TPA-induced tumors in TG.AC mice were tumorigenic when transplanted to syngeneic recipients. The v-Ha-ras transgene in the transplanted tumors was expressed at a high level. To identify possible genetic changes associated with the development of malignant tumors, explanted cells were cultured in vitro and assessed for karyotypic changes between the second and third passages by analyzing G-banded metaphase chromosomes. For comparison, skin malignancies were induced in nontransgenic FVB/N mice (parent strain) by 7,12-dimethylbenz[a]anthracene (DMBA) initiation and TPA promotion, and their G-banded metaphase chromosomes were analyzed. Trisomy (in at least 50% of about 30 metaphases) of chromosome 15 (in five of 15 tumors) and chromosome 6 (four of 15 tumors) was observed in TG.AC mice, independent of chemical treatment or tumor type. Of six tumors from DMBA/TPA-treated FVB/N mice, three had trisomy 10 or 15 (or both), and two appeared normal. The absence of trisomy 7 is notable because c-Ha-ras maps to that chromosome. The absence of trisomy 7 in the six FVB/N DMBA/TPA-induced skin malignancies contrasts with DMBA/TPA-induced karyotypic effects in SENCAR mice. Expression of the v-Ha-ras transgene may have precluded the requirement for endogenous mutant ras and allelic imbalance involving chromosome 7 in TG.AC mice, but it could not have in FVB/N mice. These results suggest the possibility that the observed trisomies are consequential, rather than causal, events in the development of TG.AC or FVB/N skin malignancies. Molecular genetic analysis will be required to understand the changes associated with tumorigenesis in this transgenic line as well as in the parent mouse line.
Mol Carcinog 1994 Dec
PMID:Cytogenetic analysis of malignant skin tumors induced in chemically treated TG-AC transgenic mice. 799 63

Numerical changes affecting chromosomes 1, 2, 3, 4, 6, 7, 8, 10, 11, 12, 16, 17, 18, and the X and Y chromosomes have been analyzed using chromosome-specific centromeric alpha-satellite repeat DNA probes in a panel of biopsies of six gastric and three esophageal adenocarcinoma and one epidermoid carcinoma of esophagus obtained at surgery. For each case, with each probe, the number of hybridization signals were determined in 200 nuclei. Hybridization of each probe to phytohemagglutinin-stimulated normal peripheral blood lymphocytes served as controls. Monosomy was defined by loss of one signal in 15% or more cells and trisomy or tetrasomy was defined by the presence of 3 or 4 signals in 7% or more cells, respectively. The Y chromosome was lost in 6 of 8 cases and monosomy 10 was seen in 5 of 10 cases. Trisomy for chromosomes 17, 8, 7, 12, 11, and 1 was seen in 4 of 10, 4 of 10, 4 of 10, 2 of 10, 2 of 8, and 2 of 10 cases, respectively, and tetrasomy for chromosome 7 was seen in 1 of 10 cases. These data show that the Y chromosome and chromosomes 10, 8, 7, 17, and 12 are most frequently involved in nondisjunctional changes in these tumors. They also document the feasibility and utility of interphase cytogenetics of gastric adenocarcinomas.
Diagn Mol Pathol 1993 Dec
PMID:Interphase cytogenetics of gastric and esophageal adenocarcinomas. 811 4

This study concerns the cytogenetics of 23 gastric carcinomas, classified histologically as intestinal or diffuse types. In carcinomas of the diffuse type, the only numerical changes observed were Y chromosome loss associated with X-chromosome disomy in four of seven male patients. A 46, XX karyotype without recognizable alterations was observed in three of five female patients, and rare structural changes in diffuse carcinomas involved chromosomes 1 and 18. In contrast, intestinal type tumors were exclusively aneuploid, with chromosome modes ranging from 48 to 84. The most consistent change was trisomy 20 in seven of 11 patients, each of which displayed a number of both single and clonal structural aberrations. Frequent structural changes were translocations involving chromosome 13 (including a putative isochromosome 13q in three of 11 patients), and alterations in chromosomes 1, 6 and 12. This study therefore suggests that diffuse and intestinal types of gastric carcinomas do not share a common sequence of genetic changes. The tumor with the worse prognosis (diffuse type) is surprisingly diploid, with uniform X-disomy in both males and females. The clinically less aggressive tumors (intestinal type) show multiple changes, both numerical and structural, of which some are reminiscent of changes seen in tumors of the lower gastrointestinal tract. Cytogenetics may thus be a valuable adjunct in establishing the diagnosis, classification, and prognosis of gastric carcinomas.
Virchows Arch B Cell Pathol Incl Mol Pathol 1993
PMID:Cytogenetic differences between intestinal and diffuse types of human gastric carcinoma. 824 74

Trisomy of chromosome 12 has been frequently described in various neoplasms, particularly in tumors of the female genitourinary tract. Fluorescence in situ hybridization with a centromeric repetitive DNA probe, specific for chromosome 12, was done to detect such cytogenic changes on frozen-tissue sections from 10 cases of ovarian sex cord stromal tumors. The case series was composed by granulosa cell tumors (four cases), fibromas (four cases), thecoma (one case), and Sertoli-Leydig cell tumor (one case). In granulosa cell tumors, the range of trisomy was 12 to 32% and in fibromas 8 to 22%, whereas in the single case of thecoma trisomy was present in 8% and in the Sertoli-Leydig cell tumor in 4% of the nuclei examined. These results represent an additional series of cases of trisomy 12 in ovarian neoplasms, namely, in ovarian sex cord stromal tumors.
Diagn Mol Pathol 1993 Jun
PMID:Detection of trisomy 12 on ovarian sex cord stromal tumors by fluorescence in situ hybridization. 826 83

Pregnant women over 35 years of age are routinely offered screening tests and karyotyping to detect Down syndrome and certain other aneuploidies because the risk of these disorders increases exponentially with maternal age. It is, however, only cost-effective to karyotype high-risk pregnancies and a substantial number of remaining aneuploidy cases go undetected. We describe a rapid, inexpensive method to detect trisomy using polymorphic small tandem repeat (STR) markers and the polymerase chain reaction (PCR) to amplify amniocyte DNA. STR patterns obtained on patients with trisomy 21, trisomy 18 and triplo-X syndromes are distinct from controls. Polymorphic trisomy genotypes either show three fragment peaks of equal intensity or two fragments at a 2:1 dosage ratio. In addition, Turner syndrome (45, X0) DNA can be distinguished from normal male DNA because it fails to amplify a Y-chromosome specific PCR marker yet contains only a single dose of X-specific STR markers. Quantitative analysis of peak heights and areas from STR markers show that the two peak patterns separate into completely non-overlapping groups. The high level of heterozygosity of most STR markers result in a predominance of heterozygous controls and trisomy patterns with multiple alleles, the easiest patterns to differentiate. Homozygosity, and hence an uninformative STR pattern, is more common in controls than in trisomy samples. We anticipate as few as three STR markers per chromosome should be over 99% informative.
Hum Mol Genet 1993 Jan
PMID:Diagnosis of Down syndrome and other aneuploidies using quantitative polymerase chain reaction and small tandem repeat polymorphisms. 849 Jun 22


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