Analysis of selected genes in neuroendocrine tumours: insulinomas and phaeochromocytomas

Abstract

Insulinomas and phaeochromocytomas are neuroendocrine tumours that may be either sporadic or manifestation of a familial cancer syndromes and are both derived from the neural crest. In the present study, gene components of different signalling pathways were investigated in sporadic human insulinomas and phaeochromocytomas to identify the responsible candidates. Ret and k-ras were tested for activating point mutations, and NF1, p53, BRCA1, nm23-H1, SDHB and SDHD for loss of heterozygosity (LOH). Twenty-two sporadic insulinomas and 15 phaeochromocytomas were analysed by the polymerase chain reaction using restriction fragment length polymorphism or dinucleotide repeat polymorphism methods. The results of our analysis demonstrate that the most frequent changes were point mutations of k-ras: 23% of insulinomas and 62% of phaeochromocytomas harboured k-ras mutations. The analysis also showed two phaeochromocytomas with point mutations of the ret oncogene. Only one insulinoma showed LOH of NF1, and another showed LOH of p53. Allelic loss of BRCA1 was detected in two insulinomas, and of nm23-H1 in another insulinoma. Allelic losses of the SDHB gene were present in two phaeochromocytoma and one insulinoma cases and allelic losses of SDHD were present in one phaeochromocytoma case. The changes observed in phaeochromocytomas were more homogenous and confined to k-ras and ret oncogenes, whereas insulinomas showed more heterogenic situation. Our findings may contribute to a better understanding of the genetic profile of neuroendocrine tumours.