PMID- 10378509
OWN - NLM
STAT- MEDLINE
DCOM- 19990709
LR  - 20061115
IS  - 0023-6837 (Print)
IS  - 0023-6837 (Linking)
VI  - 79
IP  - 6
DP  - 1999 Jun
TI  - Loss of heterozygosity in 11q13-14 regions in gastric neuroendocrine tumors not 
      associated with multiple endocrine neoplasia type 1 syndrome.
PG  - 671-7
AB  - Loss of heterozygosity (LOH) at the MEN1 gene locus at 11q13 is commonly found in 
      type II gastric carcinoid tumors, which are associated with multiple endocrine 
      neoplasia type 1 (MEN-1). In contrast, information is scanty or absent for other 
      types of gastric neuroendocrine tumors, represented by type I carcinoids 
      (associated with chronic atrophic gastritis), type III (sporadic) carcinoids, and 
      neuroendocrine carcinomas. Moreover, LOH analysis of the allelic region distal to 
      the MEN1 gene, which is postulated to contain an additional tumor suppressor gene 
      effective in MEN-1-associated and sporadic endocrine tumors, has never been 
      performed. To clarify these issues, DNA extracted from archival tissue from 25 
      type I carcinoids, 4 type III carcinoids, and 2 neuroendocrine carcinomas was 
      amplified by PCR, using primers for six polymorphic markers located on chromosome 
      11q13 (PYGM, D11S4946, and D11S913) and 11q14 (D11S916, D11S901, and D11S1365), 
      for analysis of LOH. Allelic losses in the 11q13-14 region with at least two 
      polymorphic markers were found in 12 of 25 (48%) type I carcinoids. When LOH was 
      found in the 11q13 region, it was large and continuous and extended to the most 
      telomeric marker investigated. In one tumor, retention of heterozygosity for 
      markers in the MEN1 region and LOH for distal markers were observed. No LOH was 
      found in three of four type III carcinoids. Large deletions in both the 11q13 and 
      11q14 regions were observed in both neuroendocrine carcinomas investigated. In 
      conclusion, LOH in the 11q13-14 regions is frequently found in type I carcinoids 
      and neuroendocrine carcinomas of the stomach, suggesting the involvement of the 
      MEN1 gene and/or a more telomeric tumor suppressor gene in the pathogenesis of 
      these non-MEN-1-associated neuroendocrine tumors. The low rate of LOH at 11q13-14 
      suggests the predominance of different genetic mechanisms in type III carcinoids, 
      which also differ from other types of gastric carcinoids in the lack of a 
      promoter role for gastrin.
FAU - D'Adda, T
AU  - D'Adda T
AD  - Department of Pathology, University of Parma, Italy.
FAU - Keller, G
AU  - Keller G
FAU - Bordi, C
AU  - Bordi C
FAU - Hofler, H
AU  - Hofler H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Lab Invest
JT  - Laboratory investigation; a journal of technical methods and pathology
JID - 0376617
RN  - 0 (Genetic Markers)
SB  - IM
MH  - Carcinoid Tumor/*genetics/pathology
MH  - Chromosome Mapping
MH  - *Chromosomes, Human, Pair 11
MH  - Genetic Markers
MH  - Humans
MH  - *Loss of Heterozygosity
MH  - Microsatellite Repeats
MH  - Multiple Endocrine Neoplasia Type 1/genetics/pathology
MH  - Neuroendocrine Tumors/classification/*genetics/pathology
MH  - Polymerase Chain Reaction
MH  - Polymorphism, Genetic
MH  - Stomach Neoplasms/*genetics/pathology
MH  - Trinucleotide Repeats
EDAT- 1999/06/23 00:00
MHDA- 1999/06/23 00:01
CRDT- 1999/06/23 00:00
PHST- 1999/06/23 00:00 [pubmed]
PHST- 1999/06/23 00:01 [medline]
PHST- 1999/06/23 00:00 [entrez]
PST - ppublish
SO  - Lab Invest. 1999 Jun;79(6):671-7.