PMID- 10634374
OWN - NLM
STAT- MEDLINE
DCOM- 20000203
LR  - 20041117
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 85
IP  - 1
DP  - 2000 Jan
TI  - Genotype/phenotype correlation of multiple endocrine neoplasia type 1 gene 
      mutations in sporadic gastrinomas.
PG  - 116-23
AB  - Multiple endocrine neoplasia type 1 (MEN1) gene mutations are reported in some 
      gastrinomas occurring in patients without MEN1 as well as in some other 
      pancreatic endocrine tumors (PETs). In some inherited syndromes 
      phenotype-genotype correlations exist for disease severity, location, or other 
      manifestations. The purpose of the present study was to correlate mutations of 
      the MEN1 gene in a large cohort of patients with sporadic gastrinomas to disease 
      activity, tumor location, extent, and growth pattern. DNA was extracted from 
      frozen gastrinomas from 51 patients and screened by dideoxyfinger-printing (ddF) 
      for abnormalities in the 9 coding exons and adjacent splice junctions of the MEN1 
      gene. Tumor DNA exhibiting abnormal ddF patterns was sequenced for mutations. The 
      findings were correlated with clinical manifestations of the disease, primary 
      tumor site, disease extent, and tumor growth postoperatively. Tumor growth was 
      determined by serial imaging studies. Sixteen different MEN1 gene mutations in 
      the 51 sporadic gastrinomas (31%) were identified (11 truncating, 4 missense, and 
      1 in-frame deletion). Nine of the 16 mutations were located in exon 2 compared to 
      7 of 16 in the remaining 8 coding exons (P = 0.005 on a per nucleotide basis). 
      Primary pancreatic or lymph node gastrinomas with a mutation had only exon 2 
      mutations, whereas duodenal tumors uncommonly harbored exon 2 mutations (P = 
      0.011). Similarly, small primary tumors (<1 cm) more frequently contained a 
      nonexon 2 mutation (P = 0.02). There was no difference between patients with or 
      without a mutation with respect to clinical characteristics, primary tumor site, 
      disease extent, or proportion of patients disease free after surgery. 
      Postoperative tumor growth tended to be more aggressive in patients with a 
      mutation (P = 0.09). No correlation in the rate of disease-free status or 
      postoperative tumor growth in patients with active disease to the location of the 
      mutation was seen. These results demonstrate that the MEN1 gene is mutated in 31% 
      of sporadic gastrinomas, and mutations are clustered between amino acids 66-166, 
      which differs from patients with familial MEN1, in whom mutations occur 
      throughout the gene. The presence of an MEN1 gene mutation does not correlate 
      with clinical characteristics of patients with gastrinomas, gastrinoma extent, or 
      growth pattern; however, the location of the mutation differed with gastrinoma 
      location. These data suggest that mutations in the MEN1 gene are important in a 
      proportion of sporadic gastrinomas, but the presence or absence of these 
      mutations will not identify the clinically important subgroups with different 
      growth patterns.
FAU - Goebel, S U
AU  - Goebel SU
AD  - Digestive Diseases Branch, National Institute of Diabetes and Digestive and 
      Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-1804, 
      USA.
FAU - Heppner, C
AU  - Heppner C
FAU - Burns, A L
AU  - Burns AL
FAU - Marx, S J
AU  - Marx SJ
FAU - Spiegel, A M
AU  - Spiegel AM
FAU - Zhuang, Z
AU  - Zhuang Z
FAU - Lubensky, I A
AU  - Lubensky IA
FAU - Gibril, F
AU  - Gibril F
FAU - Jensen, R T
AU  - Jensen RT
FAU - Serrano, J
AU  - Serrano J
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (DNA, Neoplasm)
SB  - IM
MH  - Base Sequence
MH  - DNA, Neoplasm/analysis/genetics
MH  - Exons/genetics
MH  - Female
MH  - Gastrinoma/*genetics
MH  - Genotype
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Molecular Sequence Data
MH  - Multiple Endocrine Neoplasia Type 1/*genetics
MH  - Mutation/*genetics
MH  - Pancreatic Neoplasms/*genetics
MH  - Phenotype
MH  - Polymerase Chain Reaction
MH  - Zollinger-Ellison Syndrome/genetics
EDAT- 2000/01/14 00:00
MHDA- 2000/01/14 00:01
CRDT- 2000/01/14 00:00
PHST- 2000/01/14 00:00 [pubmed]
PHST- 2000/01/14 00:01 [medline]
PHST- 2000/01/14 00:00 [entrez]
AID - 10.1210/jcem.85.1.6260 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2000 Jan;85(1):116-23. doi: 10.1210/jcem.85.1.6260.