SNP data from 126 hepatocellular adenomas and carcinomas
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ABSTRACT: SNP array data from 127 hepatocellular adenomas and carcinomas were used to detect recurrent copy number alterations. 48 tumors were analyzed with Illumina HumanCNV370-Duo v1.0 chips. 79 tumors were analyzed with Illumina HumanOmniExpress BeadChip.
Project description:SNP array data from 127 hepatocellular adenomas and carcinomas were used to detect recurrent copy number alterations. 48 tumors were analyzed with Illumina HumanCNV370-Duo v1.0 chips. 79 tumors were analyzed with Illumina HumanOmniExpress BeadChip.
Project description:Glycogen storage disease type 1a (GSD-1a) is caused by a deficiency in glucose-6-phosphatase-α (G6Pase-α), and is characterized by impaired glucose homeostasis and a high risk of developing hepatocellular adenomas (HCAs). A globally G6Pase-α-deficient (G6pc(-/-)) mouse model that shows pathological features similar to those of humans with GSD-1a has been developed. These mice show a very severe phenotype of disturbed glucose homeostasis and rarely live beyond weaning. We generated liver-specific G6Pase-α-deficient (LS‑G6pc(-/-)) mice as an alternative animal model for studying the long-term pathophysiology of the liver and the potential treatment strategies, such as cell therapy. LS‑G6pc(-/-) mice were viable and exhibited normal glucose profiles in the fed state, but showed significantly lower blood glucose levels than their control littermates after 6 hours of fasting. LS‑G6pc(-/-) mice developed hepatomegaly with glycogen accumulation and hepatic steatosis, and progressive hepatic degeneration. Ninety percent of the mice analyzed developed amyloidosis by 12 months of age. Finally, 25% of the mice sacrificed at age 10-20 months showed the presence of multiple HCAs and in one case late development of hepatocellular carcinoma (HCC). In conclusion, LS‑G6pc(-/-) mice manifest hepatic symptoms similar to those of human GSD-1a and, therefore, represent a valid model to evaluate long-term liver pathogenesis of GSD-1a.
Project description:Total mesorectal excision (TME) is the standard treatment for rectal cancer, while transanal endoscopic microsurgery (TEM) is a recently introduced surgical approach for the treatment of rectal adenomas. Incorrect preoperative staging before TEM is a problem. To identify genetic changes that might correlate with tumour stage and could lead to optimized treatment selection we performed a genome-wide chromosomal instability search in a homogeneous, clinical cohort of rectal tumours. 78 rectal tumours during different clinical stages were analysed with 10K single nucleotide polymorphism (SNP) arrays. Logistic regression was performed to build a quantitative model of specific chromosomal aberrations. Overall, most cases (95%) had one or more chromosomal aberrations. We observed a clear correlation between the total number of aberrations and the different tumour stages. Specifically, the chromosomal events: gain of 8q22–24, 13q and 20q, and loss of 17p and 18q12–22, were far more abundant in carcinoma than in adenoma. In adenoma fractions from cases with a carcinoma (infiltrating at least in the submucosa), twice the amount of such ‘malignant aberrations’ was observed, compared to pure adenomas. Furthermore, combined aberrations such as gain of 13q and loss of 18q were only found in adenomatous fractions of carcinomas and not in benign lesions. Based on these five genomic events associated with carcinoma, a clear distinction between adenoma and carcinoma tissue could be made. These data should be validated further in order that they may be used in preoperative staging of rectal tumours. Keywords: SNP array copy number and LOH study
Project description:SNP array data from 125 hepatocellular carcinomas were used to detect recurrent copy number alterations. 99 hepatocellular carcinomas and 86 matched normal samples were analyzed with Illumina HumanCNV370-Duo v1.0 chips. 26 hepatocellular carcinomas and 26 matched normal samples were analyzed with Illumina HumanOmniExpress BeadChip.