1/13. Rearrangement in the coding region of the MYCN gene in a subset of amplicons in a case of neuroblastoma with MYCN amplification.The MYCN gene is often amplified but rarely rearranged in neuroblastoma. We report, for the first time, a rearrangement within the MYCN coding region in a metastatic neuroblastoma in a 3-year-old boy with MYCN amplification in his primary tumor. The rearrangement occurred 46 nucleotides downstream from the ATG codon in exon 2 of MYCN. The amplification level of the rearranged copies of the MYCN gene was lower than that of the unrearranged copies of MYCN. These results indicate that the rearrangement occurred after initial MYCN gene amplification. Monochromosomal somatic cell hybrid mapping of the novel region fused to exon 2 of MYCN localized it to chromosome 2, suggesting that this rearrangement resulted from an interstitial deletion, presumably within the MYCN amplicon itself.- - - - - - - - - - ranking = 1keywords = amplification (Clic here for more details about this article) |
2/13. A fragile site at 10q23 (FRA10A) in a phenytoin-exposed fetus: a case report and review of the literature.OBJECTIVE: To report fragility at 10q23.3 in a fetus exposed to phenytoin during pregnancy. review of the literature. methods: Amniocytes were cultured in A10 (WISENT) culture medium. Molecular polymorphism studies of MTHFR gene using PCR were performed on fetal tissues. RESULTS: The fragile site was expressed in all 22 amniocyte colonies analyzed. Analysis of fetal blood showed 46,XX[98]/46,XX,fra(10)(q23.3)[3]/46,XX,del(10)(q23.3) [1]. Molecular studies of the MTHFR (methylenetetrahydrofolate reductase) gene identified a compound heterozygote genotype for two polymorphisms, 677C>T and 1298A>C. CONCLUSION: The fragility at 10q23.3 is unlikely to be due to culture condition-induced folic acid deficiency (medium contains folate). It is possible that this finding represents a previously undescribed folic acid-insensitive fragile site in the region of 10q23.3. Alternatively, the fetal cells may have had decreased folate metabolism, and the fragile site was the known folate-sensitive FRA10A. Since phenytoin has been shown to decrease MTHFR activity in mice, we postulate that the fragile site at 10q23.3 in this fetus may have arisen secondary to a combination of the polymorphisms in MTHFR and exposure to this drug, and is indeed FRA10A.- - - - - - - - - - ranking = 6.1328078992515E-5keywords = acid (Clic here for more details about this article) |
3/13. Spontaneous chromosome fragility in band 3q21, 11p11, or 11q13 of cultured bone marrow cells from two patients with hematologic disorders.Chromatid gaps and breaks clustering to band 3q21, 11p11, or 11q13 were observed prior to chemotherapy in short-term cultured bone marrow cells from two patients with hematologic disorders, one with acute monoblastic leukemia having 8 as the sole karyotypic abnormality and the other with pernicious anemia having no chromosome abnormality. The mitogen-stimulated peripheral blood lymphocytes of both patients, however, yielded a negligible frequency of chromosome aberrations. Because of no notable history of clastogen exposure in these patients, the observed chromosome fragility is most probably spontaneous, which might be correlated with the patients' physiologic condition at examination, i.e., an unusually low level of folic acid or vitamin B12, both being involved in DNA synthesis. Although band 11q13 is known to contain a common fragile site, chromosome fragility in bands 3q21 and 11p11 has not yet been reported in either normal or neoplastic cells. The present findings appear to favor the in vivo expression of chromosome fragility.- - - - - - - - - - ranking = 3.0664039496257E-5keywords = acid (Clic here for more details about this article) |
4/13. Spontaneous expression of fra(10)(q25) in bone marrow from a patient with agranulocytosis.We report on the spontaneous expression of fra(10)(q25) in bone marrow from a patient with agranulocytosis. Expression of this fragile site in both bone marrow and leukocytes was enhanced by bromodeoxyuridine (BrdU), while folic-acid-deficient medium enhanced the expression of fra(10)(q25) only in leukocytes. Variability in the expression of fra(10)(q25) in bone marrow and leukocyte cultures over an 18-month period was also found.- - - - - - - - - - ranking = 3.0664039496257E-5keywords = acid (Clic here for more details about this article) |
5/13. Heritable fragile sites and cancer: fra(16)(q22) in lymphocytes of an acute nonlymphocytic leukemia patient with inv(16)(p13q22).Fragile site testing was performed on normal peripheral blood lymphocytes from three acute nonlymphocytic leukemia patients who carried inv(16)(p13q22) in malignant cells. Cultures were treated with BrdU, distamycin A, Hoechst 33258, or folic acid deprivation to induce fragile site expression. One patient was found to be a carrier of fra(16)(q22), but the expression was observed only by Hoechst 33258 treatment.- - - - - - - - - - ranking = 3.0664039496257E-5keywords = acid (Clic here for more details about this article) |
6/13. Folate metabolism and chromosomal stability in the fragile x syndrome.Folate metabolism and the effects of folic acid on chromosome stability were studied in four related patients with the fragile x syndrome. In three adults, uptake and subsequent utilization of folate compounds for conversion of deoxyuridylate to thymidylate by marrow cells and stimulated lymphocytes, and the affinity and maximal transport velocity of erythrocyte membrane carriers, were normal. Numbers of sister chromatid exchanges and double-stranded dna breaks were comparable in cells from patients and control subjects, but both were increased after incubation in folate-deficient media. in vitro expression of the fragile site was strikingly reduced by oral folate therapy. It is concluded that the folate-sensitive chromosomal defect in this syndrome is limited to a specific site, Xq28, and there is no generalized tendency to frequent dna breaks or recombination. Although expression was modified by folic acid treatment in the patients, no consistent abnormality of folate metabolism could be identified.- - - - - - - - - - ranking = 6.1328078992515E-5keywords = acid (Clic here for more details about this article) |
7/13. Random X inactivation resulting in mosaic nullisomy of region Xp21.1p21.3 associated with heterozygosity for ornithine transcarbamylase deficiency and for chronic granulomatous disease. A young woman with normal gonadal development and mild mental retardation was found to have a small de novo interstitial deletion of most of band Xp21, karyotype designation 46,X,del(X) (pter p21.3:: p21.1 qter). Replication studies on lymphocytes and skin fibroblasts revealed that in 45% of cells the normal X was late replicating. Somatic cell hybrids between her fibroblasts and HPRT-deficient Chinese hamster cells were obtained and selected for and against retention of the active human x chromosome. In several independent hybrids the deleted X was retained in the active state. Partial ornithine transcarbamylase (ornithine carbamoyltransferase EC 2.1.3.3) (OTC) deficiency was documented by elevated urinary orotic acid excretion and increased serum glutamine after a protein load. This confirms the mapping of the structural gene for OTC to this deletion. Testing of neutrophil function revealed heterozygosity for chronic granulomatous disease (CGD) suggesting that a gene for CGD maps within the deletion. Thus, X inactivation mosaicism is also present in hepatocytes and neutrophilic granulocytes. Random X inactivation in a female with an Xp deletion has not been previously reported. The cells from this patient and the somatic cell hybrids containing her deleted x chromosome in the absence of the normal X provide material for the precise mapping of X linked genes and DNA sequences on the short arm of the human x chromosome.- - - - - - - - - - ranking = 3.0664039496257E-5keywords = acid (Clic here for more details about this article) |
8/13. Folic acid therapy in the fragile x syndrome.Two brothers with fra(X) positive X-linked mental retardation (XLMR) were treated with folic acid. Initially a double blind cross-over design was employed followed by a long-term high dose trial. A decrease in the frequency of fra(X) positive cells was observed when low folic acid culture medium was used but not when an FUdR induction system was employed. Selected behavioral characteristics improved in both while receiving folic acid. Decreased hyperactivity, greater attention span, increased motor coordination, increased quantity and quality of speech were noted. Improvement in Leiter mental age and regression after cessation of treatment was seen in one subject but not in the other. Further controlled trials with larger numbers of subjects using high doses of folic acid over longer periods of time are needed to assess the possible benefits of this experimental form of treatment.- - - - - - - - - - ranking = 0.00024531231597006keywords = acid (Clic here for more details about this article) |
9/13. A new inducible fragile site on chromosome 3(p14.2) in human lymphocytes.A fragile site on chromosome 3(p14.2) was found in lymphocytes of two unrelated patients. Expression of the trait with 6%-18% affected cells could only be demonstrated under culture conditions favouring a low concentration of folic acid. family investigations proved the maternal transmission of the cytologic marker in one case. In contrast to other fragile sites chromatid type aberrations predominated.- - - - - - - - - - ranking = 3.0664039496257E-5keywords = acid (Clic here for more details about this article) |
10/13. Coincidence between fragile site expression and interstitial deletion of chromosome 11 in a case of myelofibrosis.Cytogenetic examination of multiple peripheral blood cultures of a patient with myelofibrosis with myeloid metaplasia revealed the presence of an interstitial deletion of the long arm of chromosome 11, del(11)(q13q21). A folic acid dependent fragile site fra(11)(q13) was found in about 12% of the cells. The possible correlation between constitutional fragile site and acquired chromosomal alteration is discussed briefly.- - - - - - - - - - ranking = 3.0664039496257E-5keywords = acid (Clic here for more details about this article) |
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