Dataset Information

Distinct pathways of genomic progression to benign and malignant tumors of the liver.

ABSTRACT: We used several of the genetic lesions commonly associated with human liver tumors to reconstruct genetic progression to hepatocellular carcinoma and adenoma in mouse models. We initiated tumorigenesis with a transgene of the protooncogene MET or by hydrodynamic transfection of MET in combination with other genes into the livers of adult animals. Hepatocellular carcinoma in both instances arose from cooperation between MET and constitutively active versions of beta-catenin. In contrast, adenomas were produced by cooperation between MET and defective signaling through the transcription factor HNF1alpha. Prompted by these findings, we uncovered a coincidence between activation of the protein-tyrosine kinase encoded by MET and activating mutations of beta-catenin in a subset of human hepatocellular carcinomas. Inactivation of MET transgenes led to regression of hepatocellular carcinomas despite the persistence of activated beta-catenin. The tumors eventually recurred in the absence of MET expression, however, presumably after the occurrence of one or more events that cooperated with activated beta-catenin in lieu of MET. These results offer insight into hepatic tumorigenesis, provide mouse models that should be useful in the further study of hepatic tumorigenesis and for preclinical testing, and identify a subset of human hepatocellular carcinomas that may be susceptible to combination therapy directed against Met and the Wnt signaling pathway.

SUBMITTER: Tward AD

PROVIDER: S-EPMC1964540 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Purpose:To find potentially diagnostic texture analysis (TA) features and to evaluate the diagnostic accuracy of two-dimensional (2D) magnetic resonance (MR) TA for differentiation between hepatocellular carcinoma (HCC) and benign hepatocellular tumors in the non-cirrhotic liver in an exploratory MR-study. Materials and methods:108 non-cirrhotic patients (62 female; 41.5 ± 18.3 years) undergoing preoperative contrast-enhanced MRI were retrospectively included in this multi-center-study. TA including gray-level histogram, co-occurrence and run-length matrix features (total 19 features) was performed by two independent readers. Native fat-saturated-T1w and T2w as well as arterial and portal-venous post contrast-enhanced 2D-image-slices were assessed. Conventional reading was performed by two separate independent readers. Differences in TA features between HCC and benign lesions were investigated using independent sample t-tests. Logistic regression analysis was performed to obtain the optimal number/combination of TA-features and diagnostic accuracy of TA analysis. Sensitivity and specificity of the better performing radiologist were compared to TA analysis. Results:The highest number of significantly differing TA-features (n = 5) was found using the arterial-phase images including one gray-level histogram (skewness, p = 0.018) and four run-length matrix features (all, p < 0.02). The optimal binary logistic regression model for TA-features of the arterial-phase images contained 13 parameters with an accuracy of 84.5% (sensitivity 84.1%, specificity 84.9%) and area-under-the-curve of 0.92 (95%-confidence-interval 0.85-0.98) for diagnosis of HCC. Conventional reading yielded a significantly lower sensitivity (63.6%, p = 0.027) and no significant difference in specificity (94.6%, p = 0.289) at best. Conclusion:2D-TA of MR images is a feasible objective method that may help to distinguish HCC from benign hepatocellular tumors in the non-cirrhotic liver. Most promising results were found in TA features in the arterial phase images.

Dataset Information

Distinct pathways of genomic progression to benign and malignant tumors of the liver.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets