Carcinoma of the ampulla of Vater is a rare malignant tumour arising from the precancerous lesions, which accounts for 6%–7% of periampullary tumours and 0.2% of gastrointestinal tract malignancies. The aim of the study was to identify the chromosomal alterations and K-ras mutations and to check the methylation status in Adenomatous polyposis coli (APC) promoter region in the familial and sporadic carcinomas of the ampulla of Vater.Methods
A total of 42 samples of carcinoma of the ampulla of Vater (included 31 familial and 11 sporadic cases) and equal numbers of controls were selected which were categorised based on their age (group I<50 years; group II>50 years). Techniques including GTG-banding and PCR-RFLP were used to identify the genetic alterations. DNA methylation in APC promoter region was analysed for methylation status at the CpG regions.Results
The result revealed a high frequency of chromosomes 1p- and 12p+involved in the poorly differentiated (PD) tumour grade and an increased prevalence of the K-ras mutations at the codon 12 associated with >2 cm tumour size in the familial carcinomas of the ampulla of Vater. The APC promoter region showed hypermethylation in the CpG islands of carcinoma patients compared to controls.Conclusions
The results concluded that the chromosomes 1p- and 12p+region might play a vital role for the development of a high grade tumour and the K-ras gene mutation is an early molecular event leading to an abnormal proliferation of the cells. Methylation profiling showed that APC gene has a key role in stabilising b-catenin pathway, in which hypermethylation in APC promoter region could lead to proteasome degradation of b-catenin suggesting that APC methylation may be the potential testing for Carcinoma of the ampulla of Vater diagnosis and provide a new viewpoint in the treatment.