PMID- 9703929
OWN - NLM
STAT- MEDLINE
DCOM- 19980901
LR  - 20101118
IS  - 0250-7005 (Print)
IS  - 0250-7005 (Linking)
VI  - 18
IP  - 4A
DP  - 1998 Jul-Aug
TI  - Multiple endocrine neoplasia type 1 (MEN1): LOH studies in a affected family and 
      in sporadic cases.
PG  - 2685-9
AB  - Multiple endocrine neoplasia (Menl) is an autosomai dominant hereditary trait 
      characterized by tumors of endocrine tissues. The MEN1 gene maps to chromosome 
      llql3, has been recently isolated, and encodes a protein termed menin that is 
      ubiquitously expressed. This gene is likely to be a tumor suppressor gene, with 
      tumors developing after the inactivation of both copies of the gene in a single 
      cell. In agreement with this, 11q-deletions (loss of heterozygosity) are 
      frequently found in neoplasms from MEN1 patients. In this study, DNA from 
      family-members was extracted and analysed for 10 microsatellites flanking the 
      MEN1-gene on chromosome 11q. SSCP was used to determine the presence of 
      MEN1-mutations in several patients. DNA was extracted from paraffin blocks 
      containing tissue from 10 parathyroid tumors (4 familial and 6 sporadic) and 2 
      gastrinomas (both from patients of the Men1-family). LOH was determined by 
      comparing the autoradiographic patterns of several markers between the normal 
      tissue and the malignant tissue counterpart. All the affected individuals in the 
      MEN1-family shared one haplotype, not present in the healthy individuals. We 
      searched for mutations at the MEN1 gene (SSCP-analysis) in several affected 
      members. An SSCP-mobility shift was found at exon 9, and direct sequencing showed 
      that this corresponded to a common polymorphism at codon 418 (GAC/GAT), LOH, a 
      genetic alteration characteristic of genomic regions containing tumor suppressor 
      genes, was found in all the parathyroid tumors, but not in two gastrinomas. 
      SSCP-analysis of the MEN1-exon 9 polymorphism showed that LOH included the 
      MEN1-gene in the informative parathyroid tumors. In conclusion, LOH at 11q is 
      frequent in Menl-parathyroid tumors, either sporadic or familial, and the 
      deletion involves the MEN1-gene. In contrast, the two gastrinomas did not show 
      LOH, indicating the existence of a second mutation other than the MEN1-deletion 
      in these tumors. Our data suggest that the mechanism that drives tumorigenesis in 
      Menl either familial or sporadic, is influenced by the tissue context.
FAU - Valdes, N
AU  - Valdes N
AD  - Servicio de Endocrinologia, Hospital, Central de Asturias, Oviedo, Spain.
FAU - Alvarez, V
AU  - Alvarez V
FAU - Diaz-Cadorniga, F
AU  - Diaz-Cadorniga F
FAU - Aller, J
AU  - Aller J
FAU - Villazon, F
AU  - Villazon F
FAU - Garcia, I
AU  - Garcia I
FAU - Herrero, A
AU  - Herrero A
FAU - Coto, E
AU  - Coto E
LA  - eng
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Greece
TA  - Anticancer Res
JT  - Anticancer research
JID - 8102988
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Chromosome Deletion
MH  - Chromosome Mapping
MH  - *Chromosomes, Human, Pair 11
MH  - Exons
MH  - Family
MH  - Female
MH  - Genes, Tumor Suppressor
MH  - Genetic Linkage
MH  - Genotype
MH  - Homozygote
MH  - Humans
MH  - *Loss of Heterozygosity
MH  - Male
MH  - Microsatellite Repeats
MH  - Middle Aged
MH  - Multiple Endocrine Neoplasia Type 1/*genetics
MH  - Pedigree
MH  - Point Mutation
MH  - Polymorphism, Genetic
MH  - Polymorphism, Single-Stranded Conformational
EDAT- 1998/08/15 00:00
MHDA- 1998/08/15 00:01
CRDT- 1998/08/15 00:00
PHST- 1998/08/15 00:00 [pubmed]
PHST- 1998/08/15 00:01 [medline]
PHST- 1998/08/15 00:00 [entrez]
PST - ppublish
SO  - Anticancer Res. 1998 Jul-Aug;18(4A):2685-9.