PMID- 9935177
OWN - NLM
STAT- MEDLINE
DCOM- 19990211
LR  - 20190708
IS  - 0020-7136 (Print)
IS  - 0020-7136 (Linking)
VI  - 80
IP  - 3
DP  - 1999 Jan 29
TI  - MEN1 gene mutation analysis of sporadic adrenocortical lesions.
PG  - 373-9
AB  - To clarify the role of the MEN1 gene in the tumorigenesis of sporadic 
      adrenocortical tumors, we performed a molecular study on 35 adrenocortical 
      lesions including 6 hyperplasias, 19 adenomas and 10 carcinomas. Loss of 
      heterozygosity (LOH) of the MEN1 gene was assessed by PCR using an intragenic 
      (D11S4946) and 2 flanking microsatellite markers (D11S4936, PYGM) and/or 
      fluorescence in situ hybridization (FISH) with a 40-kb cosmid probe containing 
      the MEN1 gene. The complete coding sequence of the MEN1 gene was screened for 
      mutations using non-radioactive, PCR-based single-strand conformation 
      polymorphism (SSCP) analysis and MDE heteroduplex gel electrophoresis. PCR-LOH 
      and FISH analyses performed in 29 tumors (PCR-LOH in 4, FISH in 17 and both in 8 
      tumors) revealed allelic deletion of the MEN1 locus in 8 (27.5%) and at 11q13 in 
      9 (31%) tumors. Furthermore, the frequency of LOH at 11q13 was significantly 
      higher in adrenocortical carcinomas (60%) than in benign lesions (11%). Mutation 
      analysis of tumor samples revealed 9 polymorphisms in 7 tumors (S145S, R171Q, 
      R171Q together with L432L) but no mutations, with the exception of one 
      adrenocortical adenoma. The latter tumor contained a somatic E109X stop codon 
      mutation in exon 2 and a 5178-9G-->A splice mutation in intron 4, which was also 
      detectable in various nontumorous tissues and blood indicative of a germ-line 
      mutation. The patient, who had no clinical signs or family history of MEN1, later 
      also developed a neuroendocrine carcinoma (atypical carcinoid) of the lung. Our 
      findings indicate that inactivating mutations of the MEN1 tumor-suppressor gene 
      appear not to play a prominent role in the development of sporadic hyperplastic 
      or neoplastic lesions of the adrenal cortex and that the newly reported 
      5178-9G-->A splice mutation in intron 4 might cause a variant of the MEN1 
      phenotype.
FAU - Gortz, B
AU  - Gortz B
AD  - Department of Pathology, University of Zurich, Switzerland.
FAU - Roth, J
AU  - Roth J
FAU - Speel, E J
AU  - Speel EJ
FAU - Krahenmann, A
AU  - Krahenmann A
FAU - De Krijger, R R
AU  - De Krijger RR
FAU - Matias-Guiu, X
AU  - Matias-Guiu X
FAU - Muletta-Feurer, S
AU  - Muletta-Feurer S
FAU - Rutmann, K
AU  - Rutmann K
FAU - Saremaslani, P
AU  - Saremaslani P
FAU - Heitz, P U
AU  - Heitz PU
FAU - Komminoth, P
AU  - Komminoth P
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Int J Cancer
JT  - International journal of cancer
JID - 0042124
RN  - 0 (MEN1 protein, human)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Proto-Oncogene Proteins)
SB  - IM
CIN - Int J Cancer. 2000 Jul 15;87(2):305-7. PMID: 10861492
MH  - Adrenal Cortex/pathology
MH  - Adrenal Cortex Neoplasms/*genetics
MH  - Adrenocortical Adenoma/genetics
MH  - Adrenocortical Carcinoma/genetics
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Female
MH  - Humans
MH  - Hyperplasia/genetics
MH  - *Loss of Heterozygosity
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Proteins/*genetics
MH  - Polymerase Chain Reaction
MH  - Polymorphism, Single-Stranded Conformational
MH  - *Proto-Oncogene Proteins
EDAT- 1999/02/06 03:14
MHDA- 2000/06/20 09:00
CRDT- 1999/02/06 03:14
PHST- 1999/02/06 03:14 [pubmed]
PHST- 2000/06/20 09:00 [medline]
PHST- 1999/02/06 03:14 [entrez]
AID - 10.1002/(SICI)1097-0215(19990129)80:3<373::AID-IJC7>3.0.CO;2-B [pii]
AID - 10.1002/(sici)1097-0215(19990129)80:3<373::aid-ijc7>3.0.co;2-b [doi]
PST - ppublish
SO  - Int J Cancer. 1999 Jan 29;80(3):373-9. doi: 
      10.1002/(sici)1097-0215(19990129)80:3<373::aid-ijc7>3.0.co;2-b.