Putative tumor-suppressor gene on chromosome 11 is important in sporadic endocrine tumor formation.
Endocrine tumors arising sporadically or as a manifestation of the multiple endocrine neoplasia type I syndrome (MEN I) have been shown to have mutations on chromosome 11. These mutations can be detected at the molecular level by loss of heterozygosity (LOH) for DNA markers from chromosome 11. This study represents one of the largest collections of sporadic endocrine tumors in which LOH was systematically assessed on chromosome 11 for the loci flanking the proposed MEN I region. DNA was isolated from 39 endocrine tumors and probed with 7 DNA probes spanning the region of chromosome 11q13 from the loci PYGM to INT-2. Eleven tumors demonstrated LOH at any two loci in this region. The remaining 28 tumors showed no LOH or were noninformative at these loci. Thus, nearly 30% of these tumors showed LOH in the region (from PYGM to INT-2) that is thought to contain the MEN I gene(s). Previous studies of sporadic endocrine tumors have suggested that these tumors may arise via the same mechanism as tumors of the MEN I syndrome. Namely, these sporadic tumors are thought to result from mutations leading to genetic loss on the long arm of chromosome 11, thereby inactivating a possible tumor-suppressor gene (or genes). These findings strongly support the hypothesis that sporadic pancreatic endocrine tumors share a similar etiology of tumorigenesis with tumors of the MEN I syndrome, which principally involves deletion of a tumor-suppressor element (or elements).
Eubanks
P J
PJ
Department of Surgery, Harbor/UCLA Medical Center.
Sawicki
M P
MP
Samara
G J
GJ
Gatti
R
R
Nakamura
Y
Y
Tsao
D
D
Johnson
C
C
Hurwitz
M
M
Wan
Y J
YJ
Passaro
E
E
D015139:Blotting, Southern; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D015342:DNA Probes; D004273:DNA, Neoplasm / Q000235:genetics*; D015408:Gastrinoma / Q000235:genetics*; D016147:Genes, Tumor Suppressor / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D009377:Multiple Endocrine Neoplasia / Q000235:genetics*; D010190:Pancreatic Neoplasms / Q000235:genetics*; D010282:Parathyroid Neoplasms / Q000235:genetics*; D010911:Pituitary Neoplasms / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length
D015342:DNA Probes; D004273:DNA, Neoplasm