Biomedical subjects

Stine H Kresse

Publications and source records attributed to Stine H Kresse.

4 recordsLinked to original sources

PubMed2006

Array comparative genomic hybridization reveals distinct DNA copy number differences between gastrointestinal stromal tumors and leiomyosarcomas.

Leiomyosarcomas are spindle cell tumors showing smooth muscle differentiation. Until recently, most gastrointestinal stromal tumors (GIST) were also classified as smooth muscle tumors, but now GISTs are recognized as a separate entity, defined as spindle cell and/or epithelioid tumors localized in the gastrointestinal tract. Using microarray-based comparative genomic hybridization (array CGH), we have created a detailed map of DNA copy number changes for 7 GISTs and 12 leiomyosarcomas. Considerable gains and losses of chromosomal segments were observed in both tumor types. The most frequent aberration observed in GISTs was loss of chromosomes 14 and 22, with minimal recurrent regions in 14q11.2-q32.33 (71% of the tumors) and 22q12.2-q13.31 (100%). In leiomyosarcomas, frequent loss of chromosome 10 and 13q was observed, with minimal recurrent regions in 10q21.3 (75%) and 13q14.2-q14.3 (75%). Recurrent high-level amplification of 17p13.1-p11.2 was detected in leiomyosarcomas. Expression profiling using cDNA microarrays revealed four candidate genes in this region with high expression (AURKB, SREBF1, MFAP4, and FLJ10847). Altered expression of AURKB and SREBF1 has been observed previously in other malignancies. Hierarchical clustering of all samples separated GISTs and leiomyosarcomas into two distinct clusters. Statistical analysis identified six chromosomal regions, 1p36.11-p13.1, 9q21.11-9q34.3, 14q11.2-q23.2, 14q31.3-q32.33, 15q24.3-q26.3, and 22q11.21-q13.31, which were significantly different in copy number between GISTs and leiomyosarcomas. Our results show the potential of using array comparative genomic hybridization to classify histologically similar tumors such as GISTs and leiomyosarcomas.

Adult↗

PubMed2005

Mapping and characterization of the amplicon near APOA2 in 1q23 in human sarcomas by FISH and array CGH.

BACKGROUND: Amplification of the q21-q23 region on chromosome 1 is frequently found in sarcomas and a variety of other solid tumours. Previous analyses of sarcomas have indicated the presence of at least two separate amplicons within this region, one located in 1q21 and one located near the apolipoprotein A-II (APOA2) gene in 1q23. In this study we have mapped and characterized the amplicon in 1q23 in more detail. RESULTS: We have used fluorescence in situ hybridisation (FISH) and microarray-based comparative genomic hybridisation (array CGH) to map and define the borders of the amplicon in 10 sarcomas. A subregion of approximately 800 kb was identified as the core of the amplicon. The amplification patterns of nine possible candidate target genes located to this subregion were determined by Southern blot analysis. The genes activating transcription factor 6 (ATF6) and dual specificity phosphatase 12 (DUSP12) showed the highest level of amplification, and they were also shown to be over-expressed by quantitative real-time reverse transcription PCR (RT-PCR). In general, the level of expression reflected the level of amplification in the different tumours. DUSP12 was expressed significantly higher than ATF6 in a subset of the tumours. In addition, two genes known to be transcriptionally activated by ATF6, glucose-regulated protein 78 kDa and -94 kDa (GRP78 and GRP94), were shown to be over-expressed in the tumours that showed over-expression of ATF6. CONCLUSION: ATF6 and DUSP12 seem to be the most likely candidate target genes for the 1q23 amplification in sarcomas. Both genes have possible roles in promoting cell growth, which makes them interesting candidate targets.

Apolipoprotein A-II↗

PubMed2004

M-CGH: analysing microarray-based CGH experiments.

BACKGROUND: Microarray-based comparative genomic hybridisation (array CGH) is a technique by which variation in relative copy numbers between two genomes can be analysed by competitive hybridisation to DNA microarrays. This technology has most commonly been used to detect chromosomal amplifications and deletions in cancer. Dedicated tools are needed to analyse the results of such experiments, which include appropriate visualisation, and to take into consideration the physical relation in the genome between the probes on the array. RESULTS: M-CGH is a MATLAB toolbox with a graphical user interface designed specifically for the analysis of array CGH experiments, with multiple approaches to ratio normalization. Specifically, the distributions of three classes of DNA copy numbers (gains, normal and losses) can be estimated using a maximum likelihood method. Amplicon boundaries are computed by either the fuzzy K-nearest neighbour method or a wavelet approach. The program also allows linking each genomic clone with the corresponding genomic information in the Ensembl database http://www.ensembl.org. CONCLUSIONS: M-CGH, which encompasses the basic tools needed for analysing array CGH experiments, is freely available for academics http://www.uio.no/~junbaiw/mcgh, and does not require any other MATLAB toolbox.

Chromosomes, Artificial, Bacterial↗

PubMed2003

11q13 alterations in two cases of hibernoma: large heterozygous deletions and rearrangement breakpoints near GARP in 11q13.5.

Hibernomas are rare, benign tumors with a histological appearance resembling that of brown adipose tissue. The diagnosis of hibernomas may be difficult because some of them contain only a small number of the characteristic multivacuolated fat cells and can be mistakenly classified as well-differentiated liposarcomas. Cytogenetic information has been reported for 10 cases, showing that these tumors are characterized by structural rearrangements involving 11q13. Previous fluorescence in situ hybridization (FISH) studies revealed consistent and sometimes cryptic losses of the MEN1 region in 11q13.1. Here, we describe the molecular cytogenetic analysis of two new hibernoma cases. Both tumors showed complex rearrangements, simultaneously including translocations, inversions, and deletions affecting the pair of chromosomes 11. The translocation partners were chromosome 5 in one case and chromosomes 16 and 22 in the other case. The 11q13 region was concomitantly rearranged on both chromosomes 11. FISH studies revealed large heterozygous deletions within the 11q13 band, from 11q13.1 to 11q13.5. Genes such as PYGM, MEN1, CCND1, FGF3, ARIX, and GARP were deleted, showing that the size of the 11q13 altered region was larger than previously reported. Furthermore, both tumors had breakpoints in 11q13.5, one of them in the immediate proximity of the GARP gene. Our results suggest that rearrangements of GARP or a neighboring gene may be important for the pathogenesis of hibernomas.

Adult↗