@misc{ScholtkaSchneiderMelcheretal.2009,
  author    = {Scholtka, Bettina and Schneider, Mandy and Melcher, Ralph and Katzenberger, Tiemo and Friedrich, Daniela and Berghof-J{\"a}ger, Kornelia and Scheppach, Wolfgang and Steinberg, Pablo},
  title     = {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},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-44587},
  year      = {2009},
  abstract  = {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.},
  language  = {en}
}
@article{GereckeScholtkaLoewensteinetal.2015,
  author    = {Gerecke, Christian and Scholtka, Bettina and Loewenstein, Yvonne and Fait, Isabel and Gottschalk, Uwe and Rogoll, Dorothee and Melcher, Ralph and Kleuser, Burkhard},
  title     = {Hypermethylation of ITGA4, TFPI2 and VIMENTIN promoters is increased in inflamed colon tissue: putative risk markers for colitis-associated cancer},
  series = {Journal of cancer research and clinical oncology : official organ of the Deutsche Krebsgesellschaft},
  volume    = {141},
  journal   = {Journal of cancer research and clinical oncology : official organ of the Deutsche Krebsgesellschaft},
  number    = {12},
  publisher = {Springer},
  address   = {New York},
  issn      = {0171-5216},
  doi       = {10.1007/s00432-015-1972-8},
  pages     = {2097 -- 2107},
  year      = {2015},
  abstract  = {Epigenetic silencing of tumor suppressor genes is involved in early transforming events and has a high impact on colorectal carcinogenesis. Likewise, colon cancers that derive from chronically inflamed bowel diseases frequently exhibit epigenetic changes. But there is little data about epigenetic aberrations causing colorectal cancer in chronically inflamed tissue. The aim of the present study was to evaluate the aberrant gain of methylation in the gene promoters of VIM, TFPI2 and ITGA4 as putative early markers in the development from inflamed tissue via precancerous lesions toward colorectal cancer. Initial screening of different cancer cell lines by using methylation-specific PCR revealed a putative colon cancer-specific methylation pattern. Additionally, a demethylation assay was performed to investigate the methylation-dependent gene silencing of ITGA4. The candidate markers were analyzed in colonic tissue specimens from patients with colorectal cancer (n = 15), adenomas (n = 76), serrated lesions (n = 13), chronic inflammation (n = 10) and normal mucosal samples (n = 9). A high methylation frequency of VIM (55.6 \%) was observed in normal colon tissue, whereas ITGA4 and TFPI2 were completely unmethylated in controls. A significant gain of methylation frequency with progression of disease as well as an age-dependent effect was detectable for TFPI2. ITGA4 methylation frequency was high in precancerous and cancerous tissues as well as in inflammatory bowel diseases (IBD). The already established methylation marker VIM does not permit a specific and sensitive discrimination of healthy and neoplastic tissue. The methylation markers ITGA4 and TFPI2 seem to be suitable risk markers for inflammation-associated colon cancer.},
  language  = {en}
}
@article{MelcherHartmannZopfetal.2011,
  author    = {Melcher, Ralph and Hartmann, Elena and Zopf, Waltraud and Herterich, Sabine and Wilke, Philipp and Mueller, Ludwig and Rosler, Eduard and Kudlich, Theodor and Al-Taie, Oliver and Rosenwald, Andreas and Katzenberger, Tiemo and Scholtka, Bettina and Seibold, Stefan and Rogoll, Dorothee and Scheppach, Wolfgang and Scheurlen, Michael and Luehrs, Hardi},
  title     = {LOH and copy neutral LOH (cnLOH) act as alternative mechanism in sporadic colorectal cancers with chromosomal and microsatellite instability},
  series = {Carcinogenesis : a comprehensive survey},
  volume    = {32},
  journal   = {Carcinogenesis : a comprehensive survey},
  number    = {4},
  publisher = {Oxford Univ. Press},
  address   = {Oxford},
  issn      = {0143-3334},
  doi       = {10.1093/carcin/bgr011},
  pages     = {636 -- 642},
  year      = {2011},
  abstract  = {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.},
  language  = {en}
}