MULTIPLE HEAD AND NECK TUMORS - EVIDENCE FOR A COMMON CLONAL ORIGIN

Patients with head and neck cancers have a high (2-3%/year) incidence of second primary lesions, Clinically, these new lesions are identifie d either simultaneously with the primary lesion (synchronous) or after a period of time (metachronous), This observation has been attributed to the concept of ''field carcinogenesis,'' which is based on the hyp othesis that prolonged exposure to carcinogens leads to the independen t transformation of multiple epithelial cells at several sites, An alt ernative theory is based on the premise that any transforming event is rare; following initial transformation, the progeny of the transforme d clone spread through the mucosa and give rise to geographically dist inct but genetically related tumors, We analyzed the pattern of X-chro mosome inactivation in multiple primary tumors from eight female patie nts with head and neck cancer, In addition, we used microsatellite ana lysis to examine the pattern of allelic loss on chromosomes 9p and 3p, identified as early events in the progression of head and neck malign ancies, In four of four cases, multiple tumors demonstrated the same p attern of X-chromosome inactivation, In the remaining four cases, X-ch romosome deletions prevented interpretation (n = 3), or the androgen r eceptor locus was noninformative (n = 1). In three of nine patients, m ultiple tumors displayed the same pattern of loss of heterozygosity, t wo with identical breakpoints on chromosome 9p. In one patient, there was an identical microsatellite alteration at a 3p locus, definitive e vidence that these tumors arose from the same clone, Our findings sugg est that in at least a proportion of patients with head and neck cance rs, multiple primary tumors arise from a single clone.