1/613. Isolation and characterization of a new human breast cancer cell line, KPL-4, expressing the Erb B family receptors and interleukin-6.A new human breast cancer cell line, KPL-4, was recently isolated from the malignant pleural effusion of a breast cancer patient with an inflammatory skin metastasis. This cell line can be cultured under serum-free conditions and is tumorigenic in female athymic nude mice. Flow cytometric analysis revealed the expression of Erb B-1, -2 and -3. Dot blot hybridization showed a 15-fold amplification of the erb B-2. reverse transcription-polymerase chain reaction analysis showed a detectable level of mRNA expression of all the Erb B family receptors. In addition, all the receptors were autophosphorylated under a serum-supplemented condition. Unexpectedly, transplanted KPL-4 tumours induced cachexia of recipient mice. A high concentration of interleukin-6 (IL-6) was detected in both the culture medium and the serum of mice. The weight of tumours significantly correlated with the serum IL-6 level. The antiproliferative effect of a humanized anti-Erb B-2 monoclonal antibody, rhuMAbHER2, was investigated. This antibody significantly inhibited the growth of KPL-4 cells in vitro but modestly in vivo. Loss of mouse body weight was partly reversed by rhuMAbHER2. These findings suggest that KPL-4 cells may be useful in the development of new strategies against breast cancer overexpressing the Erb B family receptors and against IL-6-induced cachexia.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
2/613. Extra euchromatic band in the qh region of chromosome 9.Chromosomal analysis of amniotic cell culture revealed an extra euchromatic band in the variable heterochromatin region 9q12. cytogenetic analysis of the fetus was compared with the chromosomes of the parents. Using different cytogenetic banding techniques and fluorescence in situ hybridization with specific dna probes, the structural rearrangements involved were considered. The very rare variant proved to be familial. Demonstrating the inheritance of a normal individual supports the interpretation of the prenatal analysis of chromosome 9 as a variant without clinical relevance for the fetus.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
3/613. MYC amplification in two further cases of acute myeloid leukemia with trisomy 4 and double minute chromosomes.We report two cases of trisomy 4 with double minute chromosomes (dmin): one in a woman with acute myeloid leukemia (AML), French-American-British subtype M2, the other in a man with chronic myelomonocytic leukemia. In the former case, many cells without trisomy 4 but with dmin were present, a finding not observed in previously reported cases. In both cases, fluorescence in situ hybridization studies demonstrated the double minutes to be MYC amplicons. Ten cases of AML with trisomy 4 and dmin have now been described; in the five cases investigated, the dmin have been shown to be amplified MYC gene sequences.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
4/613. hemangioendothelioma of bone in a patient with a constitutional supernumerary marker.A 13-year old girl was diagnosed as having a bone hemangioendothelioma. Cytogenetic studies identified the presence of a small supernumerary marker chromosome in this patient. Classical cytogenetic methods using G-, C-, Ag-NOR-banding were supplemented by spectral karyotyping (SKY) and fluorescence in situ hybridization to reveal a karyotype 47,XX, mar.ish der(22)(D22S543 ) karyotype in cells derived from the tumor and lymphocytes. These findings suggest that the supernumerary marker chromosome originated from the proximal centromeric region of chromosome 22, and that trisomy of the region 22q11 was not associated with adverse phenotypic effects, but that the presence of trisomy 22q11 may be related to the development of this tumor.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
5/613. Identification of multiple copies of a 20q-chromosome in a case of myelodysplastic syndrome: a FISH study.In myelodysplastic syndromes (MDS) karyotypic aberrations identify subgroups of patients with distinct clinical-morphological features and can be relevant in risk assessment of developing leukemia. Often conventional cytogenetic analysis is not sufficiently informative due to the presence of partially or completely unrecognizable chromosome markers. By chromosome microdissection (MD) and fluorescence in situ hybridization (FISH) we investigated the nature of a karyotypic marker occurring in multiple copies in one case of MDS arisen in a patient previously treated for breast cancer. Results showed dicentrics derived from telomeric fusion between interstitially deleted 20q-chromosomes. The abnormal karyotype resulted into polysomy for a deleted chromosome 20q.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
6/613. B cell prolymphocytic leukaemia (B-PLL) with complex karyotype and concurrent abnormalities of the p53 and c-MYC gene.We report the cytogenetic, molecular and biological characterization of a case of B-PLL with a complex karyotype and concurrent abnormalities on the p53 and c-MYC genes. Conventional cytogenetics suggested that both 17q arms were translocated to chromosomes 1q and 14p, respectively, whereas both 17p arms were not identified. In addition, a Burkitt's-like variant translocation t(2;8) was found. Study of loss of heterozygosity at 17p13 and p53 direct sequencing demonstrated the presence of only one copy of the p53 gene. A 27 bp deletion in exon 8 that resulted in the expression of a p53 protein lacking nine amino acids from the DNA binding region was also found. To confirm the presence of one copy of the p53 gene and localize it, fluorescent in situ hybridization (FISH) studies using a p53 gene probe was performed. Only one signal of p53 was visualized. Moreover, the DAPI profile of the chromosome containing the hybridization spot for the p53 probe did correspond to the cytogenetic marker identified as der(14)t(14;17). Whole chromosome 14 paint, centromere-specific for chromosome 17 and p53 gene probes were cohybridized to the preparations. This demonstrated that the der(14) contained the 17 centromere and distally the p53 gene suggesting that the der(14) contained the short arm of chromosome 17 with the breakpoint occurring in the long arm. FISH studies confirmed the involvement of c-MYC and KAPPA in the t(2;8) translocation. To our knowledge, this is the first case of B-PLL with inactivation of the p53 gene by mutation together with a Burkitt's-like t(2;8) translocation involving the c-MYC gene. The cooperation of these genes may have conferred a growth advantage which was critical in the development of this aggressive form of B-PLL.- - - - - - - - - - ranking = 2keywords = hybridization (Clic here for more details about this article) |
7/613. Prenatal detection of extra structurally abnormal chromosomes (ESACs): new cases and a review of the literature.We present 16 cases, 10 de novo and 6 familial, in which extra structurally abnormal chromosomes (ESACs) were diagnosed prenatally and identified by fluorescence in situ hybridization (FISH) studies with follow up from birth. We review the literature on prenatally diagnosed ESACs arising de novo and suggest a management protocol for these cases.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
8/613. prenatal diagnosis of a mosaic extra structurally abnormal chromosome by spectral karyotyping.A de novo mosaic extra structurally abnormal chromosome (ESAC) was detected in 33 per cent of cultured amniotic fluid cells from a pregnant woman. Neither Q-banding nor fluorescence in situ hybridization (FISH) employing a DNA probe for nucleolar organizer region demonstrated the presence of satellites on the ESAC. spectral karyotyping (SKY) was performed in this prenatal case and led to a quick and accurate determination of the ESAC as chromosome 14 in origin. The SKY finding was confirmed by conventional FISH analysis using a chromosome 14 specific painting probe. Subsequent hybridizations with a centromeric probe and a 14q subtelomeric probe were also performed to further characterize the ESAC. Absence of (TTAGGG)n sequence on the ESAC, determined postnatally, suggested it is a ring chromosome 14. Genetic counselling concerning these findings was provided to the parents who chose to continue the pregnancy. The male infant had no apparent abnormal phenotype at birth.- - - - - - - - - - ranking = 2keywords = hybridization (Clic here for more details about this article) |
9/613. Partial trisomy 13q22-->qter and monosomy 18q21-->qter as a result of familial translocation.We report on a patient with a partial trisomy of chromosome 13q22-->qter and partial monosomy of chromosome 18q21-->qter showing distinct malformations. The phenotype of this unbalanced karyotype has not been previously described. The proband had a craniofacial dysmorphism, neck pterygium, closed fists with overlapping fingers, cutaneous appendix of the left fist, equinovarus and postaxial hexadactyly of the feet, atrial septum defect, unilateral cryptorchidism and hypertrophic pyloric stenosis. Using fluorescence in situ hybridization (FISH) the father's karyotype 46,XY.ish t(13;18)(13pter-->13q22::18q21-->18qter; 18pter-->18q21::13q22-->13qter) and the child's 46,XY.ish der(18)(18pter-->18q21::13q22-->13qter)pat were established. The mother's karyotype was normal. A risk of unbalanced offspring in carriers of a balanced reciprocal translocation depends on the length and genetic constitution of the exchanged segments. Risk figures should come only from empirical data. A phenotypically normal child with a balanced or normal karyotype could be born in the case of alternate segregation. amniocentesis should therefore be recommended in any further pregnancy.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
10/613. Clonal analysis of a case of multifocal oesophageal (Barrett's) adenocarcinoma by comparative genomic hybridization.Oesophageal adenocarcinomas arising in Barrett's epithelium occasionally present as multiple lesions. This could be due to either a multifocal presentation of the same tumour, or different neoplasms arising simultaneously in a dysplastic Barrett's oesophagus ('field cancerization'). This is a report of the genetic analysis of multiple neoplastic sites in a Barrett's oesophagus with an extensive area of dysplasia. In addition, the dysplastic Barrett's epithelium was evaluated. For the genetic screening, comparative genomic hybridization (CGH) allowed evaluation of the whole genome of each specimen. Five cancerous regions were selected and subsequently dissected from paraffin-embedded tissue blocks. The use of archival materials enabled a targeted collection of representative tumour locations. Multiple genetic aberrations were detected by CGH in all cancer sites. Losses on 3p, 4, 7q, 18q, and Y, as well as gains on 8q, 9q, 12p, 13q, 17q, 20p and X, were found in each specimen. In four out of the five lesions, simultaneous losses on 9p, 15q, and 16q, with concomitant gains on 5p, 7q, and 10p, were disclosed by CGH. Adjacent high-grade dysplastic Barrett's mucosa shared the losses on 3p, 4, 7q, 9p, 18, and Y, as well as the gains on 5p, 7q, 13q, 17q, and X, thereby confirming its precursor status. Within this single and rare case of multifocal Barrett's adenocarcinoma, a monoclonal genotype was present. This must have been caused by an extensive outgrowth of a single tumour.- - - - - - - - - - ranking = 5keywords = hybridization (Clic here for more details about this article) |
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