Different patterns of 11q allelic losses in digestive endocrine tumors.
Most foregut digestive endocrine neoplasms may be associated with the multiple endocrine type 1 (MEN-1) syndrome. In contrast, midgut/hindgut carcinoids never show such association. To investigate the pathogenetic involvement of the MEN-1 gene and of putative additional oncosuppressor gene(s) distal to it, a comparative analysis of loss of heterozygosity (LOH) at chromosome 11q13 to 11qter was performed in 27 foregut (pancreatic endocrine tumors [PETs]), 23 midgut (ileal and appendiceal), and 3 hindgut (rectal) endocrine tumors. LOH at the MEN-1 gene locus at 11q13 was observed in 52% of the 23 sporadic and in all 4 MEN-1-associated PETs and was found to consistently and continuously span to the most distal marker investigated at 11qter. In contrast, only occasional, discontinuous, and mostly interstitial LOH for 11q markers was observed in ileal (midgut) carcinoids, whereas no LOH was found in all appendiceal (midgut) and rectal (hindgut) carcinoids. The consistent extension of LOH from the MEN-1 region to 11qter in sporadic PETs suggests a mechanism of gene inactivation via chromosomal breakage and complete loss of chromosome 11q; furthermore, these results expand beyond the 11q13 region the search for additional oncosuppressor gene(s) potentially involved in the genesis of these neoplasms. The low frequency, limited extension, and discontinuous distribution of 11q deletions in midgut/hindgut carcinoids suggest that MEN-1 gene is not involved in the pathogenesis of these tumors.
D'adda
Tiziana
T
Department of Pathology and Laboratory Medicine, Section of Pathological Anatomy, University of Parma, Parma, Italy.
Pizzi
Silvia
S
Azzoni
Cinzia
C
Bottarelli
Lorena
L
Crafa
Pellegrino
P
Pasquali
Claudio
C
Davoli
Carla
C
Corleto
Vito D
VD
Delle Fave
Gianfranco
G
Bordi
Cesare
C
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002276:Carcinoid Tumor / Q000235:genetics* / Q000556:secondary; D002648:Child; D002880:Chromosomes, Human, Pair 11; D004273:DNA, Neoplasm / Q000032:analysis; D004067:Digestive System Neoplasms / Q000235:genetics* / Q000473:pathology; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D018761:Multiple Endocrine Neoplasia Type 1 / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction
D004273:DNA, Neoplasm