TY - JOUR
T1 - Identification of MEN1 gene mutations in sporadic carcinoid tumors of the lung
AU - Debelenko, Larisa V.
AU - Brambilla, Elisabeth
AU - Agarwal, Sunita K.
AU - Swalwell, Jennifer I.
AU - Kester, Mary B.
AU - Lubensky, Irina A.
AU - Zhuang, Zhengping
AU - Guru, Siradanahalli C.
AU - Manickam, Pachiappan
AU - Olufemi, Shodimu Emmanuel
AU - Chandrasekharappa, Settara C.
AU - Crabtree, Judy S.
AU - Kirn, Young S.
AU - Heppner, Christina
AU - Burns, A. Lee
AU - Spiegel, Allen M.
AU - Marx, Stephen J.
AU - Liotta, Lance A.
AU - Collins, Francis S.
AU - Travis, William D.
AU - Emmert-Buck, Michael R.
N1 - Funding Information:
C.H. is supported by a grant of the Fritz Thyssen Stiftung (Germany).
PY - 1997/12
Y1 - 1997/12
N2 - Lung carcinoids occur sporadically and rarely in association with multiple endocrine neoplasia type 1 (MEN1). There are no well defined genetic abnormalities known to occur in these tumors. We studied 11 sporadic lung carcinoids for loss of heterozygosity (LOH) at the locus of the MEN1 gene on chromosome 11q13, and for mutations of the MEN1 gene using dideoxy fingerprinting. Additionally, a lung carcinoid from a MEN1 patient was studied. In four of 11 (36%) sporadic tumors, both copies of the MEN1 gene were inactivated. All four tumors showed the presence of a MEN1 gene mutation and loss of the other allele. Observed mutations included a 1 bp insertion, a 1 bp deletion, a 13 bp deletion and a single nucleotide substitution affecting a donor splice site. Each mutation predicts truncation or potentially complete loss of menin. The remaining seven tumors showed neither the presence of a MEN1 gene mutation nor 11q13 LOH. The tumor from the MEN1 patient showed LOH at chromosome 11q13 and a complex germline MEN1 gene mutation. The data implicate the MEN1 gene in the pathogenesis of sporadic lung carcinoids, representing the first defined genetic alteration in these tumors.
AB - Lung carcinoids occur sporadically and rarely in association with multiple endocrine neoplasia type 1 (MEN1). There are no well defined genetic abnormalities known to occur in these tumors. We studied 11 sporadic lung carcinoids for loss of heterozygosity (LOH) at the locus of the MEN1 gene on chromosome 11q13, and for mutations of the MEN1 gene using dideoxy fingerprinting. Additionally, a lung carcinoid from a MEN1 patient was studied. In four of 11 (36%) sporadic tumors, both copies of the MEN1 gene were inactivated. All four tumors showed the presence of a MEN1 gene mutation and loss of the other allele. Observed mutations included a 1 bp insertion, a 1 bp deletion, a 13 bp deletion and a single nucleotide substitution affecting a donor splice site. Each mutation predicts truncation or potentially complete loss of menin. The remaining seven tumors showed neither the presence of a MEN1 gene mutation nor 11q13 LOH. The tumor from the MEN1 patient showed LOH at chromosome 11q13 and a complex germline MEN1 gene mutation. The data implicate the MEN1 gene in the pathogenesis of sporadic lung carcinoids, representing the first defined genetic alteration in these tumors.
UR - http://www.scopus.com/inward/record.url?scp=9844233708&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=9844233708&partnerID=8YFLogxK
U2 - 10.1093/hmg/6.13.2285
DO - 10.1093/hmg/6.13.2285
M3 - Article
C2 - 9361035
AN - SCOPUS:9844233708
SN - 0964-6906
VL - 6
SP - 2285
EP - 2290
JO - Human molecular genetics
JF - Human molecular genetics
IS - 13
ER -