Molecular Genetic Alterations in Primary Hepatocellular Neoplasms

NORE1B, a candidate tumor suppressor, is epigenetically silenced in human hepatocellular carcinoma

“…Many tumor types escape growth restriction by activating point mutations of Ras that render the protein resistant to inactivation [34]. However, the mutation frequency of each of the Ras oncogenes is generally below 5% in HCCs [4]. Nevertheless, the p21 Ras protein appears to be increased in most HCCs, suggesting that the Ras-MAPK pathway is hyperactive in HCCs [35,36].…”

“…While other epithelial tumors frequently harbour activating point mutations in one of the Ras-oncogenes, the frequency of K-, N-, and H-Ras mutations in HCCs is generally very low [4]. We raised the hypothesis that the activity of Ras-effector genes downstream of Ras may be altered in HCCs.…”

Multiple chromosomal abnormalities in human liver (pre)neoplasia

“…A great portion of HCCs and DNs showed LOH for the mannose 6-phosphate/insulin-like growth factor II receptor combined with deletions or mutations in the remaining allele [10]. Rb-1, E-cadherin, p73, PTEN, and Smad 2 and 4 genes are less frequently altered [2]. On the other side, genes, that may act as oncogenes, are often amplified in HCCs, as reported for c-myc or cyclin D1 [11,12].…”

“…Their frequent association with HCCs suggests a preneoplastic nature of this lesion [7]. Opinions on the severity attributed to such lesions vary widely among pathologists due to the lack of genetic and other unequivocal markers [2].…”

“…Etiological factors of HCC include infection with hepatitis B-or C-virus, chronic ethanol abuse, or dietary exposure to aflatoxin-B1 [2]. The mechanisms of liver carcinogenesis in humans are poorly understood.…”