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  -