Hbv X

The HBV X open reading frame is frequently integrated and expressed. HBV X [MLS1] can bind to the C terminus of p53, inhibits its sequence-specific DNA binding and transcriptional activation and suppresses p53-induced apoptosis

{2050, 2051, 457}. HBV X may affect a wide range of p53 functions and thereby contribute to the molecular pathogenesis of HCCs. HBV X further inhibits nucleotide excision repair {858}.

Oncogenes

Mutational activation of known oncogenes is rare. Point mutations of the c-KRAS gene and coamplification of the cyclin D1 gene were detected in only 3% {1967} and 11% {1355} of HCCs, respectively.

Recent findings, obtained by comparative genomic hybridization of amplified sequences mapped to 11q12, 12p11, and 14q12, may lead to the characterization of new genes involved in hepato-carcinogenesis {1163}.

Wnt pathway and beta-catenin

In the wingless/Wnt pathway, mutations of the p-catenin gene were detected in 26-41% of HCCs {386, 760}. Nuclear accumulation of p-catenin was observed by immunohistochemistry in all HCCs with p-catenin mutations {760}. No mutation was detected in mutation cluster region of the APC gene in any of 22 HCCs analysed {760}. Deletions on chromosomes 1p, 4q, and 16p were significantly associated with the absence of p-catenin mutation, which suggests that a p-catenin-activating mutation is involved in cases without chromosomal instability {1041}.

Genetic instability and allelic loss Frequent allelic losses have been found at loci on 1p, 4q, 5q, 8p, 11p, 13q, 16p, 16q, and 17p by restriction fragment length polymorphism analysis {2046, 200, 1970, 2203, 546, 1759, 459, 460}. Loss of heterozygosity (LOH) on chromosome 16 was detected in 52% of informative cases {1970}. The common deleted region lay between HP (16q22.1) and CTRB (16q22.3-q23.3) loci {1970}. These losses occurred more frequently in HCCs with poor differentiation, of large size, and with metastasis, and were not detected in early-stage HCCs {1970}. LOH on chromosome 16 may be involved in enhancement of tumour aggressiveness. Recent development of microsatellite markers allows an extensive allelotypic analysis {2171, 163, 1307, 1515, 659, 108}. Detailed deletion mapping revealed that allelic loss at a 1-cM-interval flanked by D4S2921 and

Prevalence of TP53 mutation 70 (codon 249; AGG > AGT); % of total HCC

Senegal (10/15)

Prevalence of TP53 mutation 70 (codon 249; AGG > AGT); % of total HCC

Senegal (10/15)

Age standardized incidence of hepatocellular carcinoma (males/105)

Average range of aflatoxin B, intake (ng/kg body weight per day)

Fig. 8.24 Correlation between TP53mutation at codon 249, dietary exposure to aflatoxin B,, and regional incidence of hepatocellular carcinoma (HCC).

Was this article helpful?

0 0
Diet Tweak System

Diet Tweak System

Trying To Lose Weight Can Be Tough. But... Not Losing Weight and Gaining What You Lost Back, Sucks. If you've ever felt that no matter what you do to lose weight nothing seems to work. If you've ever felt that there has got to be some kind of a system or way to lose weight...but just have not found it yet.

Get My Free Ebook


Post a comment