Biomedical subjects

I Nimmrich

Publications and source records attributed to I Nimmrich.

6 recordsLinked to original sources

PubMed2005

Methylation discriminators in NSCLC identified by a microarray based approach.

Aberrant DNA methylation is a frequent phenomenon in non-small cell lung cancers. We have used a microarray approach to assess the methylation status of 245 CpG positions in 59 candidate genes in 26 squamous cell carcinomas, and 22 adenocarcinomas as well as 26 normal adjacent lung tissue samples from smokers to identify genes that show a distinct methylation status difference between the two different tumour type tissues and normal adjacent tissue. Tumour tissue samples were grouped together and compared to the normal tissue sample group. A multivariate test was performed, taking into account all CpG positions that were analyzed for a particular gene, to calculate p-values for each gene based on the observed methylation difference between the two groups, p-values obtained were corrected for multiple testing. The highest degree of differential DNA methylation in squamous cell carcinoma compared to normal was observed in ARHI, MGMT, GP1bbeta, RARbeta and TMEFF2 genes, while TMEFF2, MGMT and CDKNIC genes differentiated between adenocarcinomas and normal tissue. It is of note that some of the genes for which differential methylation status was observed, have not been previously described in lung cancer. Our results provide compelling evidence that different histological types of lung cancer may be distinguished from normal tissue based on methylation profiles of specific genes.

Adenocarcinoma↗

PubMed2002

Epigenomics: genome-wide study of methylation phenomena.

Epigenetics is one of the key areas of future research that can elucidate how genomes work. It combines genetics and the environment to address complex biological systems such as the plasticity of our genome. While all nucleated human cells carry the same genome, they express different genes at different times. Much of this is governed by epigenetic changes resulting in differential methylation of our genome--or different epigenomes. Individual studies over the past decades have already established the involvement of DNA methylation in imprinting, gene regulation, chromatin structure, genome stability and disease, especially cancer. Now, in the wake of the Human Genome Project (HGP), epigenetic phenomena can be studied genome-wide and are giving rise to a new field, epigenomics. Here, we review the current and future potential of this field and introduce the pilot study towards the Human Epigenome Project (HEP).

Autoimmune Diseases↗

PubMed2001

The novel ependymin related gene UCC1 is highly expressed in colorectal tumor cells.

Normal cells differ from malignant tumor cells in the transcription levels of many different genes. Two colorectal tumor cell lines were compared with a normal colorectal cell line by differential display reverse transcription PCR to screen for tumor cell specific differentially transcribed genes. By this strategy the upregulation of a novel gene was detected designated as 'upregulated in colorectal cancer gene-1' (UCC1). The UCC1 gene transcript level is increased in cultured tumor cells and in two out of three analyzed colorectal tumor tissue specimens compared to normal cultured cells and to corresponding normal tissue samples. Remarkably, the UCC1 protein shows significant sequence similarity to the highly divergent piscine glycoproteins termed ependymins which are synthesized by leptomeningeal fibroblasts and secreted into the cerebrospinal fluid.

Amino Acid Sequence↗

PubMed2000

Seven genes that are differentially transcribed in colorectal tumor cell lines.

To identify genes which are differentially transcribed in colorectal tumor cells, we compared the two human tumor cell lines, SW480 and HCT116, with the cell line, NCM460, from normal colon epithelium as a control. Using the methods of differential display reverse transcription PCR and Northern blot hybridization, we detected the differential transcription of seven genes: cholecystokinin, reticulocalbin, Rab5 guanine nucleotide exchange factor Rabex5, caldesmon, differentiation related gene 1 (drg1), taxol resistant associated gene 3 (Trag-3) and the gene for the placental protein, diff33. The yet unidentified cDNA of the human Rabex5 gene and the 3' untranslated region of the human caldesmon gene were cloned.

Amino Acid Sequence↗

PubMed1998

A beta-catenin mutation in a sporadic colorectal tumor of the RER phenotype and absence of beta-catenin germline mutations in FAP patients.

As a signaling protein in the Wnt pathway beta-catenin plays a crucial role in the regulation of cellular proliferation. Recently, oncogenic beta-catenin mutations were described in human colorectal cancer and melanoma cell lines. Since activating mutations in the beta-catenin gene have similar effects on the biochemical level as inactivating mutations in the tumor suppressor gene APC, it is speculated that beta-catenin mutations may substitute APC gene inactivation in carcinogenesis. To address this question we analyzed twenty-three sporadic colorectal tumors of different progression states for mutations in the beta-catenin gene. Eighteen of these tumors showed the wildtype APC gene sequence. In only one of the tumors with wildtype APC a beta-catenin gene mutation was found. This tumor was of the RER (replication error) phenotype which may explain the finding that the mutation occurred in a sequential repeat motif of the beta-catenin gene. The second aim of this study was to investigate whether differences in the phenotypic variability in FAP (familial adenomatous polyposis coli) might be due to inherited alterations in the beta-catenin gene. For this we analyzed DNA from fourteen FAP patients from eight different families for germline mutations in the beta-catenin gene. We did not find any beta-catenin gene alteration in these samples. Our results indicate that somatic beta-catenin activating mutations contribute only to a minor part of human colorectal tumors and that germline beta-catenin mutations do not play a role in the variability of symptoms in FAP.

Adenomatous Polyposis Coli↗

PubMed1997

Loss of the PLA2G2A gene in a sporadic colorectal tumor of a patient with a PLA2G2A germline mutation and absence of PLA2G2A germline alterations in patients with FAP.

The Min (multiple intestinal neoplasia) mouse with a germline mutation in the adenomatous polyposis coli gene serves as an animal model for familial adenomatous polyposis coli (FAP). The number and age at onset of colorectal adenomas varies in the offspring of Min mice crossed with other strains. The murine gene for the secretory phospholipase A2 (PLA2G2A) was found to be the main candidate for these variations. To test the hypothesis of a correlation between PLA2G2A gene alterations and human tumor development, we screened 14 patients with FAP and 20 patients with sporadic colorectal cancer for germline and somatic PLA2G2A gene mutations. None of the individuals with FAP showed PLA2G2A germline alterations. However, a germline mutation was observed in one patient with an apparently sporadic colorectal tumor; the wildtype allele was somatically lost in the tumor of this patient.

Adenomatous Polyposis Coli↗