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- W2331370619 abstract "The serrated pathway in the colorectal cancer (CRC) development shows characteristic morphological and genetic differences as compared with the traditional Vogelstein9s adenoma-carcinoma sequence. According to current estimations, about 15-20% of colorectal cancers originate from serrated polyps. Activating mutations of BRAF and KRAS genes and microsatellite instability are common features in serrated polyps and cancers. To identify the driver genes behind the serrated colorectal pathway we analyzed gene copy number variations (CNVs) in 19 serrated colorectal carcinomas. DNA was extracted from fresh-frozen tissues according to standard procedures. By using the Illumina HumanCNV-370 platform we analyzed the samples for somatic copy number alterations. Raw-data were normalized using the built-in Illumina BeadStudio normalization method. To segment the LRRs (tumor vs. normal logarithmic intensity ratios) we used CBS (circular binary segmentation) and BAFsegmentation (B allele frequency) and the driver genomic alterations were searched using GISTIC algorithm. To determine genetic changes specific for serrated adenocarcinomas, the recurrent genomic variations detected were compared with those previously reported in colorectal carcinomas. The recurrent genomic alterations in serrated carcinomas overlap substantially with the previously reported alterations seen in colorectal carcinomas; losses in 1p, 4p, 4q, 5q, 8p, 17p, 18p and 18q, and the gains in 7p, 7q, 8q, 13q and 20q. However, regions that are frequently altered specifically in serrated carcinomas were also found. For example, the gains of 1q, 5p, 6p and 6q are not commonly found in primary tumors in colorectal cancer, but only in liver metastases. The frequent losses specific for serrated carcinoma occur in 3p, 6q, 9p, 11q, 16p, 22q, Xp and Xq. The highest deletion peaks observed in the current sample set are those located at 9p21.3. In summary, our whole-genome screening of serrated colorectal adenocarcinomas with SNP arrays revealed several copy number alterations previously reported in colorectal cancers. Moreover, we detected several novel copy number alterations, which were specific for the serrated adenocarcinoma. The upcoming sequence analysis of genes within regions of copy number alterations may allow detection of mutations of genes linked to serrated adenocarcinoma pathogenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-121." @default.
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- W2331370619 date "2010-04-15" @default.
- W2331370619 modified "2023-09-29" @default.
- W2331370619 title "Abstract LB-121: Serrated colorectal adenocarcinoma: Specific copy number alterations" @default.
- W2331370619 doi "https://doi.org/10.1158/1538-7445.am10-lb-121" @default.
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