p53 andp16/CDKN2 gene mutations in esophageal tumors from a high-incidence area in South Africa

Abstract

Squamous cell carcinoma of the esophagus has an uneven geographic distribution, with a high incidence in the Transkei region of Eastern Cape Province, South Africa. The precise molecular events associated with tumorigenesis of esophageal cancer in this region have not been characterized. DNA from human esophageal squamous cell carcinomas (n = 76), as well as adjacent tissue samples (n = 9) and blood (n = 50) from the same patients from the Transkei region were screened for somatic mutations. Exons 5–8 of the p53 gene and exons 1–2 of the p16/ CDKN2 gene were examined for mutations using PCR‐SSCP procedures and DNA sequence analysis. Results show that 17% of the tumors contained small deletions, insertions and point mutations, resulting in frameshifts or amino acid changes in the p53 gene. Among the mutations in the structural p16/ CDKN2 gene, 9 were point mutations, 4 were deletions and 3 were insertions. A novel C to T mutation, 25 bp upstream from the ATG start site of p16/ CDKN2, which sometimes occurs together with other structural gene variations, was found. The mutations described here are somatic in origin since none of the DNA samples from the adjacent control tissues or blood samples from the same patients had them. Int. J. Cancer 78:544–549, 1998. © 1998 Wiley‐Liss, Inc.

TP53 mutations, human papilloma virus DNA and inflammation markers in esophageal squamous cell carcinoma from the Rift Valley, a high-incidence area in Kenya

“…We report a prevalence of TP53 mutation of 39%, far below the high prevalence reported in high incidence areas of China (50-75%) [17,29-32], Northern Iran (90%) (Abedi-Ardekani et al, not published) or Western France (Normandy, 76%) [33]. Remarkably, a low prevalence of TP53 mutations has also been reported in Transkei [27]. Furthermore, the mutations identified, both in the present study and in Transkei, differ from the average mutation patterns of most cancers which are dominated by transition mutations at "hotspot" codons within CpG sites [34].…”

“…Although limited to 28 cases, this series is of interest since there is no report for ESCC in Africa except for a study in Transkei, South Africa [27]. In the present series, men and women were equally represented, a gender distribution similar to most high incidence areas where tobacco and alcohol are not the main risk factors for ESCC, such as in Northern Iran or in central China [2,7,28].…”

High-resolution mapping of molecular events associated with immortalization, transformation, and progression to breast cancer in the MCF10 model

“…The p16 protein product functions upstream of Rb, and the p14 protein blocks MDM2 inhibition of p53 activity [33]. Inactivation of the CDKN2A gene, which can include mutations, homozygous deletion, and promoter methylation, has been reported at varying frequencies [33][34][35]. Whereas CDKN2A/p16 mutations selectively inactivate the Rb pathway, deletion of the CDKN2A locus impairs both the Rb and p53 pathways.…”

Oesophageal Cancer in Africa

“…Only a few studies have examined the p53 status in oesophageal squamous cell carcinomas in patients from Africa, with most of these being confined to South Africa. Immunohistochemical (IHC) analysis indicate that p53 is overexpressed in 42-51% oesophageal squamous cell carcinomas in South African patients (29,30), whereas DNA sequencing (exons 5-8) revealed that 17-25% of the tumour samples displayed p53 mutations (30,31). As there is generally an 80% correlation between IHC and sequencing approaches to p53 status analysis (32), the frequency of p53 mutations observed in the South African samples is lower than expected.…”