Identification of MEN1 gene mutations in sporadic carcinoid tumors of the lung

Lung carcinoids occur sporadically and rarely in association with multipleendocrine neoplasia type 1 (MEN1). There are no well defined geneticabnormalities known to occur in these tumors. We studied 11 sporadic lungcarcinoids for loss of heterozygosity (LOH) at the locus of the MEN1 geneon chromosome 11q13, and for mutations of the MEN1 gene using dideoxyfingerprinting. Additionally, a lung carcinoid from a MEN1 patient wasstudied. In four of 11 (36%) sporadic tumors, both copies of the MEN1 genewere inactivated. All four tumors showed the presence of a MEN1 genemutation and loss of the other allele. Observed mutations included a 1 bpinsertion, a 1 bp deletion, a 13 bp deletion and a single nucleotidesubstitution affecting a donor splice site. Each mutation predictstruncation or potentially complete loss of menin. The remaining seventumors showed neither the presence of a MEN1 gene mutation nor 11q13 LOH.The tumor from the MEN1 patient showed LOH at chromosome 11q13 and acomplex germline MEN1 gene mutation. The data implicate the MEN1 gene inthe pathogenesis of sporadic lung carcinoids, representing the firstdefined genetic alteration in these tumors.