Biomedical subjects

Peter Schraml

Publications and source records attributed to Peter Schraml.

21 records · Page 2Linked to original sources

PubMed2002

Amplification pattern of 12q13-q15 genes (MDM2, CDK4, GLI) in urinary bladder cancer.

The chromosomal region 12q13-q15 is recurrently amplified in bladder cancer. Putative target genes located in this region include MDM2, CDK4, and GLI. To evaluate the involvement of these genes in bladder cancer, we screened a tissue microarray (TMA) containing 2317 samples by fluorescence in situ hybridization (FISH). Amplification was found for MDM2 in 5.1%, for CDK4 in 1.1%, and for GLI in 0.4% of interpretable tumors. Among tumors having amplification of at least one of these 12q13-q15 genes, 76.6% had amplification of MDM2 alone and 6.4% had amplification of CDK4 alone. Coamplifications were seen of MDM2 and CDK4 in 10.6%, and of CDK4 and GLI in 6.4%. Neither coamplifications of all three genes nor isolated GLI amplifications were found. These data suggest a prominent role of MDM2 as a 12q13-q15 amplification target in bladder cancer. However, independent CDK4 amplifications do also occur suggesting either two non-overlapping amplification sites or else a minimal overlapping region between MDM2 and CDK4 perhaps containing another yet unknown oncogene. The frequency of amplification increased significantly from stage pTa to pT1-4 (P<0.04) and from low to high grade (P<0.005). These data are consistent with a high level of genetic instability in invasively growing and high-grade bladder tumors.

Chromosomes, Human, Pair 12↗

PubMed2002

VHL mutations and their correlation with tumour cell proliferation, microvessel density, and patient prognosis in clear cell renal cell carcinoma.

Mutations of the von Hippel-Lindau (VHL) gene are considered critical for the initiation of clear cell renal cell carcinoma. The VHL protein is involved in regulation of the cell cycle and neo-vascularization. In this study, the association of VHL mutations with tumour cell proliferation, angiogenesis, and clinical outcome was analysed in 113 clear cell renal cell carcinomas. The degree of angiogenesis and tumour cell proliferation was immunohistochemically determined by counting microvessels (microvessel density, anti-CD34 antibody) and cells with proliferating activity (Ki-67 labelling index, MIB-1 antibody). Forty-eight different VHL sequence alterations were found in 38 of 113 patients (34%) by direct sequencing. Nineteen VHL mutations were frameshifts and nonsense mutations, predicted to change the open reading frame of VHL. These 'loss-of-function' mutations correlated with worse prognosis in univariate analysis (p=0.02). Tumour grade, stage, microvessel density, and tumour cell proliferation were not associated with VHL alterations. These findings may indicate that 'loss-of-function' VHL mutations are involved in the progression of a clear cell renal cell carcinoma subset, whereas regulation of angiogenesis and proliferation of renal carcinoma in vivo is apparently not directly influenced by VHL alterations.

Analysis of Variance↗

PubMedDate not supplied

Molecular and clinicopathological analysis of ovarian carcinomas with and without microsatellite instability.

BACKGROUND: Microsatellite instability (MSI) occurs in sporadic ovarian carcinomas. This study tests the hypothesis that ovarian carcinomas arising through the mutator pathway have distinctive clinical and molecular features that affect clinical outcome. MATERIALS AND METHODS: The MSI status was evaluated in 66 ovarian carcinomas and 11 epithelial ovarian tumors of low malignant potential. For the analysis with the microsatellite markers, a fluorescence-based PCR method was employed and the prognostic significance of the MSI status was assessed. DNA copy number changes in tumors with and without MSI were analyzed by comparative genomic hybridization. RESULTS: High-frequency MSI (MSI-H) was found in 30% of the carcinomas, whereas low-frequency MSI (MSI-L) occurred in 32%. In LMP tumors, only MSI-L was detected (18%). There was a trend for tumors with MSI-H and MSI-L to have a poor prognosis, but this relationship did not reach significance (p=0.09 and p=0.07, respectively). MSI-H in carcinomas was significantly associated with poor differentiation (p=0.03) and higher clinical stage (p=0.03). No correlation was found between different histological types of ovarian carcinoma and the microsatellite status. In a multivariate analysis, MSI at the dinucleotide repeat D5S346 was found to be of independent prognostic significance (p<0.008) for disease-specific survival. There was no association between the total number of genetic aberrations per tumor and the MSI status. CONCLUSION: Microsatellite instability is a relatively common event in ovarian carcinoma. The data indicate that instability of a single microsatellite marker on chromosome 5 (D5S346) might be indicative of disease progression when detected in early clinical stages.

Adaptor Proteins, Signal Transducing↗