Identical clonality of sporadic gastrinomas at multiple sites

Gastrinomas are neuroendocrine neoplasms that occur sporadically and in pat ients with multiple endocrine neoplasia type 1 (MEN1), In MEN1, multiple ga strinomas have been shown to arise by independent clonal events (Debelenko, et al,, Cancer Res., 57: 2238-2243, 1997). The purpose of the present stud y was to analyze clonality in 20 sporadic gastrinomas from eight patients i n whom the tumor was present in at least two separate sites. A combination of methods was used to assess clonality, including MEN1 gene mutation analy sis, loss of heterozygosity analysis of the MEN1 locus, and analysis of X-c hromosome inactivation at the human androgen receptor locus (human androgen receptor analysis). In three patients, a semantic MEN1 gene mutation was d etected in the tumor. Identical mutations were found in other tumors at dif ferent sites within the same patients. Human androgen receptor analysis in three informative patients and loss of heterozygosity analysis in five pati ents revealed identical clonal patterns in the tumors from multiple sites i n each patient, We conclude that sporadic gastrinomas at multiple sites are monoclonal and that MEN1 gene alterations in gastrinomas occur before the development of tumor metastases.