TY  - GEN
A1  - Scholtka, Bettina
A1  - Schneider, Mandy
A1  - Melcher, Ralph
A1  - Katzenberger, Tiemo
A1  - Friedrich, Daniela
A1  - Berghof-Jäger, Kornelia
A1  - Scheppach, Wolfgang
A1  - Steinberg, Pablo
T1  - A gene marker panel covering the Wnt and the Ras-Raf-MEK-MAPK signalling pathways allows to detect gene mutations in 80% of early (UICC I) colon cancer stages in humans
N2  - Background: Very recently a gene marker panel that allows the mutational analysis of APC, CTNNB1, B-RAF and K-RAS was conceived. The aim of the present study was to use the 4-gene marker panel covering the Wnt and Ras-Raf-MEK-MAPK signalling pathways to determine the percentage of sporadic colorectal carcinomas (CRC) carrying at least one of the four above-mentioned genes in a mutated form alone and/or in combination with microsatellite instability (MSI) and to compare the sensitivity of the gene marker panel used in this study with that of gene marker panels previously reported in the scientific literature. Methods: CTNNB1 and B-RAF were screened by PCR-single-strand conformation polymorphism analysis and K-RAS gene mutations by restriction fragment length polymorphism analysis. For the mutational analysis of the APC gene mutation cluster region (codons 1243–1567) direct DNA sequencing was performed. The U.S. National Cancer Institute microsatellite panel (BAT25, BAT26, D2S123, D5S346 and D17S250) was used for MSI analysis. Results: It could be shown that about 80% of early stage CRC (UICC stages I and II) and over 90% of CRC in the UICC stage IV carried at least one mutated gene and/or showed MSI. No significant increase in the gene mutation frequencies could be determined when comparing tumours in the UICC stage I with those in UICC stage IV. Conclusions: When compared with previously published gene marker panels the 4-gene marker panel used in the present study shows an excellent performance, allowing to detect genetic alterations in 80–90% of human sporadic CRC samples analyzed.
T3  - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - paper 120 
KW  - Colorectal carcinomas
KW  - K-RAS
KW  - Microsatellite instability
KW  - Oncogenes
KW  - Tumour suppressor genes
Y1  - 2009
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus-44587
ER  - 
TY  - JOUR
A1  - Melcher, Ralph
A1  - Hartmann, Elena
A1  - Zopf, Waltraud
A1  - Herterich, Sabine
A1  - Wilke, Philipp
A1  - Mueller, Ludwig
A1  - Rosler, Eduard
A1  - Kudlich, Theodor
A1  - Al-Taie, Oliver
A1  - Rosenwald, Andreas
A1  - Katzenberger, Tiemo
A1  - Scholtka, Bettina
A1  - Seibold, Stefan
A1  - Rogoll, Dorothee
A1  - Scheppach, Wolfgang
A1  - Scheurlen, Michael
A1  - Luehrs, Hardi
T1  - LOH and copy neutral LOH (cnLOH) act as alternative mechanism in sporadic colorectal cancers with chromosomal and microsatellite instability
JF  - Carcinogenesis : a comprehensive survey
N2  - Background and aims. Tumor suppressor genes are often located in frequently deleted chromosomal regions of colorectal cancers (CRCs). In contrast to microsatellite stable (MSS) tumors, only few loss of heterozygosity (LOH) studies were performed in microsatellite instable (MSI) tumors, because MSI carcinomas are generally considered to be chromosomally stable and classical LOH studies are not feasible due to MSI. The single nucleotide polymorphism (SNP) array technique enables LOH studies also in MSI CRC. The aim of our study was to analyse tissue from MSI and MSS CRC for the existence of (frequently) deleted chromosomal regions and tumor suppressor genes located therein. Methods and results. We analyzed tissues from 32 sporadic CRCs and their corresponding normal mucosa (16 MSS and 16 MSI tumors) by means of 50K SNP array analysis. MSS tumors displayed chromosomal instability that resulted in multiple deleted (LOH) and amplified regions and led to the identification of MTUS1 (8p22) as a candidate tumor suppressor gene in this region. Although the MSI tumors were chromosomally stable, we found several copy neutral LOHs (cnLOH) in the MSI tumors; these appear to be instrumental in the inactivation of the tumor suppressor gene hMLH1 and a gene located in chromosomal region 6pter-p22. Discussion. Our results suggest that in addition to classical LOH, cnLOH is an important mutational event in relation to the carcinogenesis of MSS and MSI tumors, causing the inactivation of a tumor suppressor gene without copy number alteration of the respective region; this is crucial for the development of MSI tumors and for some chromosomal regions in MSS tumors.
Y1  - 2011
U6  - https://doi.org/10.1093/carcin/bgr011
SN  - 0143-3334
VL  - 32
IS  - 4
SP  - 636
EP  - 642
PB  - Oxford Univ. Press
CY  - Oxford
ER  -