CASE REPORT: An inherited APC mutation in the first reported Australian case of Turcot's syndrome

Abstract

The objective of this study was to determine the inherited gene mutation responsible for the first reported Australian case of Turcot's syndrome. DNA was extracted from the archival tissue blocks obtained at the time of the patient's original surgery and from fresh blood samples obtained from selected family members. These were analysed for mutations of the familial adenomatous polyposis gene (APC). Analysis of DNA from the archival blocks and from each of the affected family members revealed an inherited 5 base pair deletion at codon 1061 of APC. In this case, the central nervous system tumour represents an extracolonic manifestation of familial adenomatous polyposis. The underlying inherited mutation of APC has been identified. In some cases of Turcot's syndrome, other genes appear to be involved. Recent literature examining the molecular basis of Turcot's syndrome is reviewed.

A distinct splice form of APC is highly expressed in neurones but not commonly mutated in neuroepithelial tumours

“…Hamilton et al 12 first reported an APC patient whose medulloblastoma contained a homozygous protein truncating mutation. The increased risk of central nervous system (CNS) tumours in APC patients, the high expression of APC in developing and adult rodent CNS,39-42 and scattered mutational reports12 43 suggest that a loss of APC function can be a causative factor in the development of neuroepithelial tumours. This also provides a rationale for assaying sporadic neuroepithelial tumours for APC mutations.…”