National Cancer Institute®
Last Modified: July 1, 2002
UI - 11689590
AU - Nishimura S; Sato T; Ueda H; Ueda K
TI - Acute myeloblastic leukemia as a second malignancy in a patient with hereditary retinoblastoma.
SO - J Clin Oncol 2001 Nov 1;19(21):4182-3
UI - 11887617
AU - Plomp AS; Bergen AA; Hulsman CA; de Jong PT
TI - [Changing perception of hereditary eye diseases]
SO - Ned Tijdschr Geneeskd 2002 Feb 23;146(8):345-50
AD - Klinisch geneticus, Interuniversitair Oogheelkundig Instituut KNAW, Meibergdreef 47, 1105 BA Amsterdam.
The authors present the cases of two parents with Usher syndrome type I who appeared to have normal offspring, and two families, one with autosomal dominant retinoblastoma and a RB1-gene mutation and one with primary open angle glaucoma and a myocilin gene mutation, in whom DNA-analysis was used to see whether check-ups were needed. The field of ophthalmogenetics comprises many disorders, both congenital and those with a later onset. Mendelian, mitochondrial, as well as multifactorial heredity is seen. Recent progress in this field, especially in molecular genetics, has created new possibilities, but some situations appear to be more complex than previously assumed. Particularly if there is genetic heterogeneity or multifactorial inheritance, possibilities for counselling and DNA analysis remain limited.
UI - 11905807
AU - Knudson AG
TI - Two genetic hits (more or less) to cancer.
SO - Nat Rev Cancer 2001 Nov;1(2):157-62
AD - Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA. email@example.com
Most cancers have many chromosomal abnormalities, both in number and in structure, whereas some show only a single aberration. In the era before molecular biology, cancer researchers, studying both human and animal cancers, proposed that a small number of events was needed for carcinogenesis. Evidence from the recent molecular era also indicates that cancers can arise from small numbers of events that affect common cell birth and death processes.
UI - 11783178
AU - Liu J; Liu H; Liang Y
TI - [Effect of compound Chinese drug bailong on the expression of tumor suppressor genes and relationship with prekallikrein activator signal pathway in human gastric carcinoma BGC82-3 cell line]
SO - Zhongguo Zhong Xi Yi Jie He Za Zhi 1999 Oct;19(10):613-6
AD - Department of Cell Biology, Medical University, Beijing Institute for Cancer Research (100034).
OBJECTIVE: To study the effect of compound Chinese drug Bailong on the transcription of Cyclin Dependent Kinase Inhibitor (CKI) p16INK4a, p21 and Rb, c-myc genes, and the relationship between gene expression and cAMP-PKA pathway. METHODS: Using the traditional molecular biology methods (cell synchronization, molecular hybridization--Western blotting, Northern blotting, etc.) examine the gene expression. RESULTS: Bailong promoted the expression (both mRNA and protein) of p16INK4a obviously in G1 phase cells. When prekallikrein (PKA) inhibitor was added in the cells which were treated by Bailong, the mRNA and protein level of p16INK4a decreased. It was shown that the inhibited proliferation of BGC82-3 cell by Bailong may come from the enhanced p16INK4a gene expression in G1 phase. Being same as p16INK4a, tumor suppressor genes Rb, p21 and oncogene c-myc expression were all affected by Bailong. When PKA inhibitor was added, the results were reversed. CONCLUSION: Bailong can affect many anticancer genes (including p16INK4a, p21 and Rb genes) and oncogenes (including c-myc) transcription by regulating cAMP-PKA pathway.
UI - 12117173
AU - Raizis A; Clemett R; Corbett R; McGaughran J; Evans J; George P
TI - Improved clinical management of retinoblastoma through gene testing.
SO - N Z Med J 2002 May 24;115(1154):231-4
AD - Department of Molecular Pathology, Christchurch School of Medicine.
AIMS: To investigate the relative benefits of retinoblastoma gene testing over conventional ophthalmological screening methods in a New Zealand setting, and to determine the importance of tumour material in resolving germline status. METHODS: Three cases of gene testing are described to illustrate the clinical advantages over conventional ophthalmological screening. To determine the role of tumour material in resolving germline status, 24 New Zealand families were tested, of which tumour material was available for eight. RESULTS: In the three cases reported, we found genetic testing of the RB1 gene resulted in clinically significant benefits and cost savings. When fresh tumour was available for high molecular weight DNA extraction, germline status was resolved in 8/8 (100%) cases. In these cases tumour mutations were not present in the corresponding peripheral blood DNA, indicating that the tumours were sporadic. In the absence of tumour DNA, mutations were identified in only 8/13 (62%) heritable cases. Germline status remains unresolved in all of the three cases of unilateral tumour without a family history or tumour DNA. CONCLUSIONS: Our experience indicates that retinoblastoma gene testing has significant benefits to the affected individuals and their families in New Zealand. Moreover, DNA extracted from fresh tumour allows retinoblastoma germline status in most cases to be defined. Without rumour material, the germline status of potentially sporadic cases will remain undetermined since the absence of detectable RB1 coding region mutations does not exclude all possible mutations in the RB1 gene, which is too large for DNA analysis. A lack of conclusive results will mean that infants will be subjected to the unnecessary inconvenience of surveillance under general anaesthesia.
UI - 12016586
AU - Klutz M; Brockmann D; Lohmann DR
TI - A parent-of-origin effect in two families with retinoblastoma is associated with a distinct splice mutation in the RB1 gene.
SO - Am J Hum Genet 2002 Jul;71(1):174-9
AD - Institut fur Humangenetik, Universitatsklinikum Essen, Germany.
We have identified a splice-site mutation (IVS6+1G-->T) in the RB1 gene, in two unrelated families with incomplete-penetrance retinoblastoma. Analysis of RNA from white blood cells showed that this mutation causes skipping of exon 6. Although this deletion results in a frameshift, most carriers of the mutation did not develop retinoblastoma. Interestingly, the relative abundance of the resultant nonsense messenger RNA varies between members of the same family and is either similar to or considerably lower than the transcript level of the normal allele. Moreover, variation of relative transcript levels is associated with both the sex of the parent that transmitted the mutant allele and phenotypic expression: All eight carriers with similar abundance of nonsense and normal transcript have received the mutant allele from their mother, and only one of them has developed retinoblastoma; by contrast, all eight carriers with reduced abundance of the nonsense transcript have received the mutant allele from their father, and all but two them have retinoblastoma. After treatment with cycloheximide, the relative abundance of transcripts from paternally inherited mutant alleles was partly restored, thus indicating that posttranscriptional mechanisms, rather than transcriptional silencing, are responsible for low levels of mutant messenger RNA. Our data suggest that a specific RB1 mutation can be associated with differential penetrance, on the basis of the sex of the transmitting parent.
UI - 12115515
AU - Fitzek MM; Dahlberg WK; Nagasawa H; Mukai S; Munzenrider JE; Little JB
TI - Unexpected sensitivity to radiation of fibroblasts from unaffected parents of children with hereditary retinoblastoma.
SO - Int J Cancer 2002 Jun 10;99(5):764-8
AD - Department of Cancer Cell Biology, Harvard School of Public Health, Boston, MA 02116, USA.
The response to ionizing radiation was examined in diploid skin fibroblasts derived from 5 patients with hereditary type retinoblastoma as well as their parents. Unexpected sensitivity to cell killing, as measured by clonogenic survival, as well as enhanced radiation-induced G(1) arrest were observed in at least 1 parental fibroblast strain in all 5 families. In all cases, parental strains were equally or more radiosensitive than the probands. The mutation of the retinoblastoma gene (RB) determined in 4 of 5 probands was either absent from the parental cells, as expected from the negative family histories, or identical, in 1 father who was a known carrier. In the fifth family, the family history was negative for retinoblastoma. We hypothesize that the increased parental cell sensitivity to radiation suggests the presence of an as yet unrecognized genetic event occurring in 1 or both parents of children with retinoblastoma. Whether it increases mutability of the RB locus or other loci or interacts with RB is conjectural. Copyright 2002 Wiley-Liss, Inc.
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