De novo germ-line mutation of APC gene in periampullary carcinoma with familial adenomatous polyps - A novel familial case report in South India

Periampullary carcinoma is a malignant tumour arising from the ampulla of vater. Adenomatous polyposis coli (APC) gene has a key role in stabilizing β-catenin pathway, in which hypermethylation in APC gene could lead to proteasome degradation of β-catenin. The aim of this case report is to identify the APC gene mutation and its influence on β-catenin pathway in patient with periampullary carcinoma. A 51-year-old woman was diagnosed with yellow discolouration of sclera, passing deep yellow coloured urine and pruritus. A family history of ovarian cancer had been reported in her mother. Her radiological, pathological and laboratory examination confirmed periampullary carcinoma. She underwent whipple's pancreaticoduodenectomy, and the histopathology of the resected specimen showed a well differentiated adenocarcinoma involving the ampulla of vater. Further, the tumour region was subjected to genetic screening by polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP), cytogenetic analyses such as karyotyping and immunohistochemical techniques. These results showed non-sense mutation in APC gene at codon 1309, chromosomal alterations at 5q21 and irregular accumulation of β-catenin in nuclear membrane. The family history revealed a strong association of ovarian cancer (maternal) with a similar APC gene mutation. We conclude that periampullary carcinoma patient exhibit FAP due to de novo germ-line mutation of APC gene that engenders an inactivation of β-catenine/TCF mediated transcription function, which is linked with a family history of ovarian cancer.