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Role of disease‐causing genes in sporadic pancreatic endocrine tumors: MEN1 and VHL
Author(s) -
Moore Patrick S.,
Missiaglia Edoardo,
Antonello Davide,
Zamò Alberto,
Zamboni Giuseppe,
Corleto Vito,
Falconi Massimo,
Scarpa Aldo
Publication year - 2001
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.1180
Subject(s) - men1 , multiple endocrine neoplasia , insulinoma , germline mutation , cancer research , tumor suppressor gene , neuroendocrine tumors , biology , loss of heterozygosity , allele , germline , somatic cell , mutation , pancreas , medicine , gene , endocrinology , genetics , carcinogenesis
Pancreatic endocrine tumors (PETs) occur in association with multiple endocrine neoplasia type 1 (MEN1) and von Hippel‐Lindau (VHL) syndromes caused by germline alterations in MEN1 and VHL , respectively. It is thus expected that these genes will also be altered in a proportion of sporadic PETs. Indeed, MEN1 is altered in about 25% of nonfamilial PETs, although no mutations have been found in VHL . For all clinical subtypes, the frequency of allelic loss on chromosome arm 11q mirrors observed mutational frequencies, with the exception of nonfunctional tumors (NF‐PETs), in which mutations have been reported in only 8% of cases. As allelic loss on 11q is the most frequent event found in these neoplasms, this low frequency is somewhat puzzling, particularly in light of the fact that most MEN1‐associated PETs are nonfunctioning. To clarify the role of these genes in sporadic PETs, we analyzed 31 sporadic NF‐PETs, nine insulinomas, and one VIPoma for alterations in MEN1 and VHL . As somatic mutations were observed in eight (26%) of the NF tumors and in one insulinoma, it would therefore appear unlikely that an additional tumor suppressor gene related to sporadic PET pathogenesis is located on 11q. One insulinoma also had a somatic mutation in VHL , and thus this gene may also be altered in these neoplasms, albeit in a small proportion of cases. © 2001 Wiley‐Liss, Inc.