Background and objectives: The molecular pathogenesis of phaeochromocytoma has not yet been fully established. The p16 tumour suppressor gene is often inactivated in a wide variety of primary human malignancies, including tumours of ectodermal origin. We have therefore examined the status of the p16 gene in a series of phaeochromocytomas.
Design: We studied tumour and constitutive DNA from 26 phaeochromocytoma patients. Twenty-two cases were of sporadic tumours whereas four patients had a hereditary form of the disease. Four tumours were malignant. We performed a semiquantitative multiplex PCR in which the p16 gene was coamplified with an unrelated sequence as an internal control. Standards were constructed by mixing DNA from cell lines with a known p16 status to simulate various degrees of p16 loss. Deletion of the p16 gene was determined by densitometry, measuring the ratio of intensity of the two resulting bands as an indication of the relative abundance of the two templates in the sample.
Results: No homozygous deletion of the p16 tumour suppressor gene was found in any of the phaeochromocytoma samples.
Conclusions: We have demonstrated that the p16 gene is not deleted in sporadic, hereditary, malignant or benign forms of phaeochromocytomas, and therefore probably does not play a role in the pathogenesis of this tumour. However, because of the small number of malignant cases analysed, we cannot exclude a low frequency of p16 deletions in this subset of tumours.