The multiple endocrine neoplasia type I gene locus is involved in the pathogenesis of type II gastric carcinoids.
OBJECTIVE
Both gastrin and genetic factors were suggested to underlie the pathogenesis of multiple gastric enterochromaffin-like (ECL) cell carcinoids. To assess the role of genetic alterations in carcinoid tumorigenesis, loss of heterozygosity (LOH) at the locus of the multiple endocrine neoplasia type 1 (MEN-1) gene was studied in gastric carcinoids of patients with MEN-1 and chronic atrophic type A gastritis (A-CAG), as well as in sporadically arising intestinal carcinoids.


METHODS
DNA extracted from archival tissue sections of 35 carcinoid tumors was assessed for LOH with eight polymorphic markers on chromosome 11q13. A combined tumor and family study was performed in 1 patient with MEN-1-Zollinger-Ellison syndrome (ZES).


RESULTS
LOH at 11q13 loci was detected in 15 of 20 (75%) MEN-1-ZES carcinoids, and each ECL-cell carcinoid with LOH showed deletion of the wild-type allele. Only 1 of 6 A-CAG carcinoids displayed LOH at the MEN-1 gene locus, and none of the 9 intestinal and rectal carcinoids showed 11q13 LOH.


CONCLUSIONS
Gastric ECL-cell carcinoid is an independent tumor type of MEN-1 that shares a common developmental mechanism (via inactivation of the MEN-1 gene) with enteropancreatic and parathyroid MEN-1 tumors. Further analysis of sporadic and A-CAG carcinoids is needed to elucidate genetic factors involved in their tumorigenesis.
Debelenko
L V
LV
Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Emmert-Buck
M R
MR
Zhuang
Z
Z
Epshteyn
E
E
Moskaluk
C A
CA
Jensen
R T
RT
Liotta
L A
LA
Lubensky
I A
IA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002276:Carcinoid Tumor / Q000235:genetics* / Q000473:pathology; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D005756:Gastritis / Q000235:genetics; D017353:Gene Deletion; D005819:Genetic Markers; D006801:Humans; D007414:Intestinal Neoplasms / Q000235:genetics; D008297:Male; D008875:Middle Aged; D018761:Multiple Endocrine Neoplasia Type 1 / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D015043:Zollinger-Ellison Syndrome / Q000235:genetics / Q000473:pathology
D004273:DNA, Neoplasm; D005819:Genetic Markers