| 1. |
- Helou, K, et al.
(författare)
-
A dual-color FISH framework map for the characterization of the Sai1 tumor suppression region on rat chromosome 5
- 2000
-
Ingår i: Genes, Chromosomes and Cancer. - : John Wiley & Sons, Inc.. - 1045-2257 .- 1098-2264. ; 27:4, s. 362-372
-
Tidskriftsartikel (refereegranskat)abstract
- The analysis of cell hybrids between malignant mouse hepatoma cells and normal rat fibroblasts has previously demonstrated the critical role of a deletion in rat chromosome 5 (RNO5) that was related to an anchorage independent phenotype. Those hybrids that were anchorage independent displayed loss of the entire RNO5 or an interstitial deletion in RNO5. These findings suggested that a putative tumor suppressor gene, Sai1 (suppression of anchorage independence 1), was located within the deleted region. To explore the molecular basis of the tumor suppressor activity of the Sai1 region, we analyzed the RNO5q23-q36 region with several genes and microsatellite markers that could be assigned to the region, as well as with new markers derived by representational difference analysis (RDA) or by microdissection. Dual-color FISH was used to construct a detailed physical map of the entire RNO5. These new data can be used to connect the physical and linkage maps in the rat, as well as to identify the details of the comparative map with other mammalian species including humans and mice. Using as FISH reagents genomic YAC, P1, or phage lambda clones corresponding to RNO5 markers, the order and unique positions of 18 markers could be established. The map provided a framework for the detailed characterization of the deletion found in anchorage independent hybrids. All markers within the bands RNO5q31.3-q35 were shown to be lost, including known cancer-related genes such as Ifna (5q32), Cdkn2a, -b (5q32), Jun (5q34), and Cdkn2c (5q35). However, the aberration in the deletion chromosome turned out to be more complex than originally thought in that we detected the presence of a paracentric inversion in addition to a deletion. The inversion led to the juxtaposition of the gene markers Tal2 (5q24.1) and Cd30lg (5q24.3). The framework map will provide the basis for the detailed physical YAC clone contig mapping of this region, and facilitate the identification and characterization of the Sai1 locus.
|
|
| 2. |
- Andersen, MK, et al.
(författare)
-
Balanced chromosome abnormalities inv(16) and t(15;17) in therapy-related myelodysplastic syndromes and acute leukemia: Report from an international workshop
- 2002
-
Ingår i: Genes, Chromosomes and Cancer. - : Wiley. - 1045-2257 .- 1098-2264. ; 33:4, s. 395-400
-
Tidskriftsartikel (refereegranskat)abstract
- The Workshop identified 48 unselected patients with therapy-related myelodysplastic syndrome or acute myeloid leukemia (t-MIDS/t-AML) and inv(16), and 41 patients with t(15; 17) after chemotherapy (CT) and/or radiotherapy (RT) for a malignant or nonmalignant disease. The primary diseases were: breast cancer, 33 patients; lymphomas, 24 patients; various other solid tumors, 30 patients; and nonmalignant diseases, 2 patients. The general type of previous therapy was RT only in 10 patients with an inv(16) and in 12 patients with a t(15; 17), alkylating agents plus topoisomerase 11 inhibitors in 24 patients with an inv (16) and in 18 patients with a t(15; 17), topoisomerase 11 inhibitors only in 5 patients with an inv(16) and in 2 patients with a t(15; 17), alkylating agents only in 6 patients in each subgroup, and other types of chemotherapy in 3 patients in each subgroup. Most CT-treated patients (69%) also received RT. The latency period to development of t-MDS/t-AML was short: a median of 22 months in patients with inv(16) and 29 months in patients with t(15; 17). Twenty-six patients (54%) with an inv(16) and 17 patients (41%) with a t(15; 17) had additional cytogenetic abnormalities, which were unrelated to age and survival in both subgroups. Trisomy of chromosomes 8, 21, and 22 and del(7q) were the most frequent additional abnormalities in the inv(16) subgroup, whereas +8, -5, and del(16q) were most frequent in the t(15; 17) subgroup. The disease was overt t-AML in 38/48 patients (79%) with an inv(16) and in 38/41 patients (93%) with a t(15; 17). Thirty-three of 39 intensively treated patients (85%) with an inv(16) obtained a complete remission, whereas 24 of 35 intensively treated patients (69%) with a t(15; 17) obtained a complete remission. The median overall survival of intensively treated patients was 29 months in both cytogenetic subgroups. In the inv(16) subgroup, patients younger than 55 years of age had a longer survival when compared with older patients (P = 0.006). The study supports the observation that t-MDS/t-AML with inv(16) and t(15; 17) is often associated with prior therapy with topoisomerase 11 inhibitors; however, a notable finding was the high frequency of treatment with only radiotherapy, 29% of t(15; 17) and 21 % of inv(16). Response rates to intensive chemotherapy in this study were comparable to those of de novo disease.
|
|
| 3. |
- Behboudi, Afrouz, 1967, et al.
(författare)
-
High-density marker loss of heterozygosity analysis of rat chromosome 10 in endometrial adenocarcinoma.
- 2001
-
Ingår i: Genes, chromosomes & cancer. - : John Wiley & Sons. - 1045-2257 .- 1098-2264. ; 32:4, s. 330-41
-
Tidskriftsartikel (refereegranskat)abstract
- Endometrial cancer is a disease with serious impact on the human population, but not much is known about genetic factors involved in this complex disease. Female BDII rats are genetically predisposed to spontaneous endometrial carcinoma, and the BDII inbred strain provides an experimental animal model for endometrial carcinoma development. In the present study, BDII females were crossed with males from two nonsusceptible inbred rat strains. Endometrial adenocarcinomas (EACs) developed in a proportion of the F1 and F2 progeny. We screened 18 EAC solid tumors and 9 EAC cell cultures for loss of heterozygosity (LOH) using fluorescent-PCR-based marker allelotyping methodology with 47 microsatellite markers covering the proximal part of rat chromosome 10 (RNO10). Conclusive evidence was obtained for LOH/deletion involving about 56 cM in the proximal part of RNO10 in DNA from six out of seven informative tumor cell cultures. Analysis of the solid tumors confirmed the presence of LOH in this part of RNO10 in 14 of 17 informative tumors. However, from the studies in the solid tumors it appeared that in fact three separate segments in the proximal part of RNO10 were affected. These three LOH/deletion regions were located approximately in cytogenetic bands 10q11-12, 10q22, and 10q24.
|
|
| 4. |
- Hashemi, J, et al.
(författare)
-
Haplotype analysis and age estimation of the 113insR CDKN2A founder mutation in Swedish melanoma families.
- 2001
-
Ingår i: Genes, chromosomes & cancer. - : Wiley. - 1045-2257 .- 1098-2264. ; 31:2, s. 107-16
-
Tidskriftsartikel (refereegranskat)abstract
- Germline mutations in the CDKN2A tumor suppressor gene located on 9p21 have been linked to development of melanomas in some families. A germline 3-bp insertion in exon 2 of CDKN2A, leading to an extra arginine at codon 113 (113insR), has been identified in 17 Swedish melanoma families. Analysis of 10 microsatellite markers, spanning approximately 1 Mbp in the 9p21 region, showed that all families share a common allele for at least one of the markers closest to the CDKN2A gene, suggesting that the 113insR mutation is an ancestral founder mutation. Differences in the segregating haplotypes, due to meiotic recombinations and/or mutations in the short-tandem-repeat markers, were analyzed further to estimate the age of the mutation. Statistical analysis using a maximum likelihood approach indicated that the mutation arose 98 generations (90% confidence interval: 52-167 generations), or approximately 2,000 years, ago. Thus, 113insR would be expected to have a more widespread geographic distribution in European and North American regions with ancestral connections to Sweden. Alternatively, CDKN2A may lie in a recombination hot spot region, as suggested by the many meiotic recombinations in this narrow approximately 1-cM region on 9p21.
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
- MacGrogan, D, et al.
(författare)
-
Structural integrity and expression of the L3MBTL gene in normal and malignant hematopoietic cells
- 2004
-
Ingår i: Genes, Chromosomes and Cancer. - : Wiley. - 1045-2257 .- 1098-2264. ; 41:3, s. 203-213
-
Tidskriftsartikel (refereegranskat)abstract
- The human L3MBTL gene is located in 20q12, a region that is commonly deleted in myeloproliferative disorders (MPD), myelodysplastic syndromes (MDS), and acute myeloid leukemia (AML). L3MBTL is highly homologous to the D-lethal(3) malignant brain tumor [D-l(3)mbt] gene, which is a putative tumor-suppressor gene (TSG) identified in Drosophila and which is closely related to the Drosophila sex combs on midleg (SCM) protein, a member of the Polycomb group (PcG) family of transcriptional repressors. To examine whether L3MBTL functions as a "classic" TSG in human hematologic malignancies, we screened a panel of 17 myeloid leukemia cell lines and peripheral blood or bone marrow samples from 29 MDS and 13 MPD patients for mutations in the entire L3MBTL coding sequence, including intron/exon splice junctions. No mutations were identified, although two single nucleotide differences were found (in intron 14 and in exon 15), which were interpreted as polymorphic changes. We used real-time RT-PCR to quantify the level of L3MBTL mRNA in various normal myeloid and lymphoid cell populations. L3MBTL is expressed in normal CD34+ bone marrow cells, and we found that the pattern of L3MBTL expression was similar to that of BMIl, a well-studied PcG gene with oncogenic activity, suggesting that L3MBTL and BMII may be co-regulated during hematopoiesis. The expression of L3MBTL mRNA in 30 of 35 cell lines and 13 of IS AML samples was comparable to the level of L3MBTL expression in the normal cell populations. However, five leukemia cell lines showed no L3MBTL expression, and two of the AML samples showed aberrant L3MBTL expression. These data suggest that L3MBTL is not mutated in MDS or MPD. However, given the known dosage effects of PcG proteins in regulating gene expression, reduced or absent L3MBTL expression may be relevant in some cases of myeloid leukemia. (C) 2004 Wiley-Liss, Inc.
|
|
| 9. |
|
|
| 10. |
|
|
