Molecular genetic findings in gastric carcinoid suggest possible neurofibromin/Ras pathway involvement in carcinoid pathogenesis

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Introduction: The molecular pathogenesis of gastrointestinal carcinoid tumours is poorly understood. We have been undertaking molecular genetic investigations of a young woman with neurofibromatosis type 1 (NF1) in whom a gastric carcinoid tumor was detected following an episode of gastrointestinal bleeding. She was otherwise relatively mildly affected by NF1. In NF1, gastric carcinoids have been found previously only in patients with other predisposing factors, which were absent in this patient.

Aim(s): Genetic investigations were undertaken in order to determine whether this carcinoid tumor may have been caused by an underlying NF1 genetic lesion.

Materials and methods: Molecular genetic analysis of the patient’s peripheral blood DNA was carried out by dHPLC and automated capillary sequencing. Quantitative fluorescent PCR (QF-PCR) analysis of intragenic and flanking chromosome 17 polymorphic genetic markers was undertaken to detect loss of heterozygosity (LOH). PCR and sequencing of tumor DNA, around the site of the germline mutation, was performed to determine which allele was lost in the tumor DNA. Microsatellite instability tests and tumor cell cytogenetic analysis were also undertaken.

Conference: 7th Annual ENETSConcerence (2010)

Presenting Author: Tobias E

Authors: Tobias E, Fletcher A, Cooke A, Traynor J, Onen N,

Keywords: gastric carcinoid, neurofibromatosis, NF1, LOH, genetic, Ras,