Biomedical subjects

T Liehr

Publications and source records attributed to T Liehr.

116 records · Page 7Linked to original sources

PubMed1994

Localization of the human beta-catenin gene (CTNNB1) to 3p21: a region implicated in tumor development.

The human beta-catenin locus (CTNNB1) was mapped by in situ fluorescence analysis to band p21 on the short arm of chromosome 3, a region frequently affected by somatic alterations in a variety of tumors. PCR primers for the genomic amplification of beta-catenin sequences were selected on the basis of homology to exon 4 of the Drosophila armadillo gene. Analysis of a panel of somatic cell hybrids confirmed the localization of beta-catenin on human chromosome 3. Furthermore, exclusion mapping of three hybrids carrying defined fragments of the short arm of human chromosome 3 allowed us to determine the position of the CTNNB1 locus close to the marker D3S2 in 3p21.

Adenomatous Polyposis Coli Protein↗

PubMed1994

Tetrasomy 8 as a clonal anomaly in myeloid neoplasias.

Tetrasomy of chromosome 8 as a sole anomaly is apparently extremely rare in acute non-lymphocytic leukemia (ANLL): Only two cases have been reported, one of ANLL (M5b) with this karyotype. Very recently, another case was reported of a myelodysplastic syndrome (MDS) with isolated tetrasomy 8. We report tetrasomy 8 in four cases of ANLL, two of them with M5 and one with M1 subtype. Although in the latter case, tetrasomy 8 was evident in all karyotypes analyzed, in all other cases it constituted a subpopulation of cells other than those with trisomy 8 and those with a normal karyotype (in only one case another change was evident in the karyotype). Using fluorescence in situ hybridization (FISH), the proportion of tetrasomic cells was determined in interphase nuclei. By this technique, small cell populations (3-9%) were detected in three additional trisomy cases. An additional "control" group of five trisomy cases did not show a significant population of tetrasomic interphase nuclei. The data show that tetrasomy 8, if present as a sole anomaly in ANLL, may play a rather specific role for the subtype, and probably for the progression of myeloid neoplasia as well.

Adult↗

PubMed1992

A study of ten small supernumerary (marker) chromosomes identified by fluorescence in situ hybridization (FISH).

In seven cases additional minute chromosomes studied by FISH were identified as no. 3, 11, 15, 18, 21 and X. Findings were unexpected except for partial trisomy 21 in an adolescent with minor features of Down's syndrome. Moreover, an i(18p) in a mentally retarded dysmorphic child and an idic(15) in a child with Fallot tetralogy was confirmed. In a child with r(21), a supernumerary marker was shown to be derived from no. 21, while in the mother an additional marker idic(22) was noted.

Amniocentesis↗

PubMed1992

Typical and partial cat eye syndrome: identification of the marker chromosome by FISH.

Three children are reported with typical cat eye syndrome (CES) and three more children with partial CES because of absence of coloboma, in which the supernumerary marker chromosome was studied by FISH. Using a genomic library, and also a centromeric and particularly a cosmid probe of 22q11, partial tetrasomy was shown in all cases.

Anus, Imperforate↗

PubMedDate not supplied

Human and mouse RAD17 genes: identification, localization, genomic structure and histological expression pattern in normal testis and seminoma.

Recently, the human orthologue to the cell cycle checkpoint genes rad17 (Schizosaccharomyces pombe) and RAD24 (Saccharomyces cerevisiae), called HRAD17, has been isolated and localized to chromosome 4. Independently, we have isolated the HRAD17 transcript and mapped it to chromosome 5q13 between the CCNB1 and BTF2p44cen genes. Furthermore, we have identified the complete exon-intron structure of HRAD17. The gene is organized into 14 exons, the translation initiation site lies within exon 2, and the stop codon within exon 14. Two further HRAD17 pseudogenes, HRAD17P1 and HRAD17P2, were identified on chromosomes 7p21 and 13q14.3, respectively, encompassing exons 3-14 and bearing 84% and 93% homology, respectively. Additionally, we have isolated the coding region of the mouse orthologue, Mrad17, and mapped it on chromosome 13 between Ccnb1 and Btf2p44, the same two genes between which it maps in human. The predicted Mrad17 polypeptide encompasses 687 amino acids and shows 89% similarity to HRAD17. Both genes are most highly expressed in testis compared to all other tissues, as shown by Northern blot hybridization. Histological studies, based on in situ hybridization with radioactively labeled antisense HRAD17 riboprobes, showed a strong expression within the germinal epithelium of the seminiferous tubuli in normal testis whereas in testicular tumors (seminomas) only weak, diffuse signals were seen. In light of the known function of the yeast orthologue at meiotic and mitotic checkpoints, as well as the strong expression in testis and weak expression in seminomas, we suggest a putative involvement of HRAD 17 in testicular tumorigenesis.

Animals↗

PubMedDate not supplied

I-FISH control of CGH-detected gain of DNA sequence copy number in oral squamous cell carcinomas (OSCC).

Interphase fluorescence in situ hybridization (I-FISH) was used to control the gain of genomic material in 21 human oral squamous cell carcinomas (OSCC) which had been detected by comparative genomic hybridization (CGH). DNA probes for 3q27, for 5p15.2, and for the protooncogenes c-myc (8q24) and c-abl (9q34), were used for I-FISH examination of the interphase nuclei of paraffin sections of the tumors. The corresponding alphoid DNA probes for the centromeric regions of the respective chromosomes and a probe on 5q served as controls of aneusomy. Previous examinations with int2 (11q13) and erbB2 (17q11.2-13) were included for comparison. I-FISH analysis detected a gain of 3q27 in 17, of 5p15.2 in 7, of c-myc in 14, of c-abl in 10, and formerly, of int2 in 12 and of erbB2 in 10 of the examined tumors. There was an overall confirmation of the CGH findings by the I-FISH data in 63% (36-83% depending on the studied chromosomal site), and vice versa of 76% of the I-FISH results by the CGH data. Based on these results it is recommended to use a combination of both I-FISH and CGH for the detection of genomic changes in human solid tumors as the data obtained by both techniques ideally complete each other. For this reason both techniques have now enriched the spectrum of molecular histopathology.

Adult↗

PubMedDate not supplied

Comparative interphase cytogenetics using FISH on human ovarian carcinomas.

Analyses using fluorescence in situ hybridization (FISH) were performed on cytogenetic slides of 25 human ovarian carcinomas. Biotinylated alphoid DNA probes were used for the monocolor and bicolor detection of chromosomes #1, #7, #8, #11, #12, #17 and #20 in interphase nuclei of the target cell material. Specific loss of chromosomes #17 and #20 was the most significant finding in aberrant cell populations of the tumors, as was gain of chromosomes #7, #1, #8 and #11. By the use of probe combinations, the presence of combined gains and losses of several chromosomes within the same cell subpopulations could be shown in a series of tumors, while in others the significant numerical chromosome abnormalities found characterized various different cell populations. In summary, FISH could be shown to be a powerful tool of interphase cytogenetics, provided that its limitations are considered conscientiously.

Adult↗

PubMedDate not supplied

Chromosomal heterogeneity of aneuploid leukemic cell populations detected by conventional karyotyping and by fluorescence in situ hybridization (FISH).

Beside the frequent aneusomies of chromosomes # 7 and # 8 gains or losses of several other chromosomes are found in bone marrow cells of leukemia patients. Chromosomal heterogeneity of interphase cell populations was studied by fluorescence in situ hybridization (FISH) with centromeric DNA probes for chromosomes #2, #3, #4, #6, #9, #11, #12, #15, #16, #17, #18, #20, as well as X and Y which were found to be aberrant by routine karyotyping of 28 cases of various malignant hematopoietic diseases. Particularly, the data obtained by both routes of analysis were compared quantitatively. As the most prominent result, all aberrations found by classical karyotyping were redetected by interphase cytogenetics, but additional aberrant clones could be observed among the interphase cell populations. The frequencies of the cell clones with hypersomies were in general higher in metaphase than in interphase, and, vice versa, monosomic cells were found more frequently in interphase than in metaphase. Single aberrant karyotypes in all cases were redetected as microclones of interphase cells. Interphase cytogenetics using FISH, therefore, was shown not only to be a reliable measure of the genomic heterogeneity of leukemic cell populations but, in addition, to be a valuable and informative supplement to routine leukemia cytogenetics with regard to the detection of microclones which, later on, could dominate the progression of the malignant disease.

Adolescent↗