Biomedical subjects

Lars O Baumbusch

Publications and source records attributed to Lars O Baumbusch.

3 recordsLinked to original sources

PubMed2006

Expression of full-length p53 and its isoform Deltap53 in breast carcinomas in relation to mutation status and clinical parameters.

BACKGROUND: The tumor suppressor gene p53 (TP53) controls numerous signaling pathways and is frequently mutated in human cancers. Novel p53 isoforms suggest alternative splicing as a regulatory feature of p53 activity. RESULTS: In this study we have analyzed mRNA expression of both wild-type and mutated p53 and its respective Deltap53 isoform in 88 tumor samples from breast cancer in relation to clinical parameters and molecular subgroups. Three-dimensional structure differences for the novel internally deleted p53 isoform Deltap53 have been predicted. We confirmed the expression of Deltap53 mRNA in tumors using quantitative real-time PCR technique. The mRNA expression levels of the two isoforms were strongly correlated in both wild-type and p53-mutated tumors, with the level of the Deltap53 isoform being approximately 1/3 of that of the full-length p53 mRNA. Patients expressing mutated full-length p53 and non-mutated (wild-type) Deltap53, "mutational hybrids", showed a slightly higher frequency of patients with distant metastasis at time of diagnosis compared to other patients with p53 mutations, but otherwise did not differ significantly in any other clinical parameter. Interestingly, the p53 wild-type tumors showed a wide range of mRNA expression of both p53 isoforms. Tumors with mRNA expression levels in the upper or lower quartile were significantly associated with grade and molecular subtypes. In tumors with missense or in frame mutations the mRNA expression levels of both isoforms were significantly elevated, and in tumors with nonsense, frame shift or splice mutations the mRNA levels were significantly reduced compared to those expressing wild-type p53. CONCLUSION: Expression of p53 is accompanied by the functionally different isoform Deltap53 at the mRNA level in cell lines and human breast tumors. Investigations of "mutational hybrid" patients highlighted that wild-type Deltap53 does not compensates for mutated p53, but rather may be associated with a worse prognosis. In tumors, both isoforms show strong correlations in different mutation-dependent mRNA expression patterns.

Alternative Splicing↗

PubMed2004

CGH-Explorer: a program for analysis of array-CGH data.

SUMMARY: CGH-Explorer is a program for visualization and statistical analysis of microarray-based comparative genomic hybridization (array-CGH) data. The program has preprocessing facilities, tools for graphical exploration of individual arrays or groups of arrays, and tools for statistical identification of regions of amplification and deletion.

Computer Graphics↗

PubMed2004

LEC1, FUS3, ABI3 and Em expression reveals no correlation with dormancy in Arabidopsis.

Dormant Arabidopsis seeds require stratification and light for germination. To study gene expression during establishment, maintenance and release of dormancy, various Arabidopsis ecotypes that are different in their degree of dormancy were investigated; three nsm mutants that lack the stratification-dependency, and the precocious germination and reduced dormancy of the abi3-1 mutant (insensitive to ABA). Genes examined by mRNA abundance include LEC1, FUS3 and ABI3, transcription factors that are major regulators of embryo development and, at least indirectly, play some role in the control of dormancy. Moreover, the late embryogenesis marker genes, AtEm1 and AtEm6, were examined in relation to the state of dormancy. The expression of LEC1, FUS3 and ABI3 mRNA is only marginally different during seed development in various strong or moderate dormancy wild types, nsm mutants and abi3-1. Therefore, it is unlikely that these transcription factors directly control the establishment of dormancy in Arabidopsis. Sole and various combina tions of light, temperature, and after-ripening regimes that alter germination behaviour were examined to determine if the expression of ABI3, AtEm1 and AtEm6 mRNAs were correlated with dormancy-breaking processes. ABI3 expression is influenced by cold and light, in a similar way in both dormant and non-dormant wild-type seeds. ABI3 transcript abundance in the nsm1 and nsm2 mutants is higher and in the nsm5-1 mutant is marginally lower than in wild-type seeds, but changes due to temperature and light factors are very similar to those that occur in wild-type seeds. The abundances of AtEm1 and AtEm6 mRNAs are equally affected by imbibition and cold temperature in mature and after-ripened seeds. The LEA transcript abundances for AtEm1 and AtEm6 are reduced in nsm mutants in a common, ABI3-independent pathway.

Arabidopsis↗