Alterations of the MEN1 Gene in Sporadic Parathyroid Tumors1
Filip Farnebo,
Bin Tean Teh,
Soili Kytölä,
Ann Svensson,
Catherine Phelan,
Kerstin Sandelin,
Norman W. Thompson,
Anders Höög,
Günther Weber,
Lars-Ove Farnebo and
Catharina Larsson
Department of Molecular Medicine, Endocrine Tumor Unit (F.F.,
B.T.T., A.S., C.P., C.L.), Department of Molecular Medicine, Clinical
Genetics Unit (G.W.), Department of Clinical Pathology (A.H.) and
Department of Surgery (F.F., A.S., K.S., L.-O.F.), Karolinska Hospital,
S-171 76 Stockholm, Sweden; the Department of Clinical Genetics, Oulu
University Hospital (S.K.), Kajaanintie 50, 90220 Oulu, Finland; and
the Department of Surgery, University of Michigan Hospital (N.T.), TC
2920-D, Ann Arbor, Michigan 48109
Address all correspondence and requests for reprints to: Dr. Filip Farnebo, Department of Molecular Medicine, Endocrine Tumor Unit, Karolinska Hospital CMM L8:01, S-171 76 Stockholm, Sweden. E-mail:
filip.farnebo{at}cmm.ki.se
Primary hyperparathyroidism is a common endocrine disease thatalso
occurs in a number of inherited disorders, including multipleendocrine
neoplasia type 1 (MEN1). Loss of heterozygosity (LOH)in the
MEN1 region on chromosome 11q13 has been found in 30%
ofsporadic parathyroid tumors, making the recently cloned
MEN1gene a prime candidate for involvement in
parathyroid tumorigenesis.Using LOH and single strand conformation
analysis, we screened45 sporadic tumors from 40 patients for
alterations involvingthe MEN1 gene. Thirteen tumors
showed LOH at 11q13, and in 6of these cases, somatic mutation of the
MEN1 gene was detected.In tumors without LOH, no
mutations were detected. The mutationsconsisted of 3 small deletions,
1 insertion, and 2 missensemutations that had not been reported in
MEN1 patients or parathyroidtumors previously. Using messenger
ribonucleic acid in situhybridization, the expression
of the MEN1 gene was studied.There was no difference in
expression between normal and tumortissue. In conclusion, the findings
of inactivating mutationin tumors with LOH at 11q13 confirm the role
of the MEN1 tumorsuppressor gene in a subset of
sporadic parathyroid tumors.
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