Multiple head and neck tumours and their genetic relationship.

Second primary tumours represent one of the major causes of failure in the treatment of head and neck cancer. Advances in early diagnosis and treatment have improved the patient's disease-specific survival. However, the increase in the occurrence of second primary tumours negatively influences the patient's chance of long-term survival. To understand the molecular events underlying the appearance of head and neck multiple tumours, the clinical history has been evaluated in 2 patients both of whom developed 3 primary tumours of the head and neck. To establish the genetic relationship between the different head and neck cancers which had developed in these 2 patients, loss of heterozygosity was investigated using microsatellite markers located on chromosomes 3p, 9p, 11q, 13q, and 17p. These markers were selected as they frequently demonstrate loss of heterozygosity in head and neck cancer. The following markers were used: D3S1234, D3S1300, D9S170, D11S490, and D17S158. Primer sequences were obtained from the genome database for all of these markers. The third tumour that developed in the first patient, 13 years after the primary, showed loss of heterozygosity on chromosome 17p (in the locus for the gene TP53), which was not present in the previous tumours. All tumours in the second patient showed heterozygosity of chromosome 11 at the locus D11S490. These 2 cases show that multiple tumours can be derived from a genetic alteration of a subclone from previous tumours or from an independent preneoplastic cell clone present in the head and neck mucosa.