Hepatocellular carcinoma (HCC) is a leading cause of death in both Africa and Asia. It is
multifactorial in aetiology and complex in its pathogenesis. Genes that might affect tumour
progression, invasion, and metastasis are good candidates to investigate in attempting to
understand the transformation process. The p53, RBI, BRCA1, BRCA2, WT1 and Ecadherin
genes were analysed for allelic imbalance/loss of heterozygosity (LOH),
polymorphisms, and mutations. Tumour and non-tumorous liver tissue from 25 southern
African blacks were examined, using polymerase chain reaction restriction fragment length
polymorphisms (PCR-RFLP) and PCR-single stranded conformational polymorphisms
(SSCP), sequencing, and Southern blotting techniques. Allele frequencies for
polymorphisms at the WEI, D13S137, D13S120, D13S127, D17S855, D16S301, and
D16S260 loci were determined in 20 random African blacks using microsatellite analysis to
determine allele frequencies, polymorphism information content (PIC) and diversity (H)
values. To our knowledge this has not been done previously for these loci in this
population. The chromosomal region l i p 13, containing the VV77 gene, and the gene itself
has been reported to be deleted in 4.5% of HCCs. LOH was detected at the WT1 locus for
1/13 HCCs (8%) in this study. The RBI gene has been described to be mutated in 32.4%
(China), 33.3% (Korea), 29% and 50% tJapan), and 27% (Australia), of advanced stage
HCCs. In our study LOH at this locus was found in 3/19 HCCs (16%). Our finding of
LOH at the BRCA2 locus in 2/20 HCCs (10%) supports the previously proposed notion that
BRCA2 may function as a tumour suppressor gene in a hormone-related pathway in the
liver, and that it may in some way be involved in HCC. No conclusive findings were made
for any o f the other loci. Microsatellite instability was detected in 3/22 (14%) individuals.
We propose that microsatellite/genomic instability may play a role in a subset of HCCs
only. O f this population, 27 % had the specific p53 codon 249 AGG-AGT mutation in some
tumour and non-tumorous liver. This was expected as the great majority of the individuals
were from Mozambique, a country where heavy aflatoxin exposure is prevalent. All the loci
examined in the allele frequency studies proved to be highly informative, showing high PIC
and ED values, and should therefore be useful in population studies.
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:wits/oai:wiredspace.wits.ac.za:10539/14696 |
| Date | 22 May 2014 |
| Creators | Martins, Carla Suzana Pinto |
| Source Sets | South African National ETD Portal |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Format | application/pdf |
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