title: Characterization of high-grade neuroendocrine tumors of the lung in relation to menin mutations.
abstract: It has been suggested that mutations in the menin gene play a role in the development of multiple endocrine neoplasia type 1 (MEN1)-associated and of sporadic forms of low- and intermediate-grade neuroendocrine tumors of the lung. In the present study, eight tumor specimens of large cell neuroendocrine carcinoma (LCNEC) and 13 of small cell lung cancer (SCLC), which represent a high-grade category of neuroendocrine tumors, were examined for the potential involvement of menin alterations as well as for the expression of various neuroendocrine markers and p53 and Rb abnormalities. All specimens expressed multiple neuroendocrine markers as expected and almost invariably carried p53 and Rb alterations. Unexpectedly, however, mutations in the menin gene were not detected in any of the high-grade neuroendocrine tumors examined. We thus conclude that menin mutations do not play a crucial role in the pathogenesis of high-grade subsets, in contrast to their suggested significant role in the development of low- and intermediate-grade subsets. Interestingly, loss of heterozygosity (LOH) in the menin gene appeared to be more prevalent in LCNEC (50%) than in SCLC (22%), suggesting a possible distinction between SCLC and LCNEC.
authors.affiliation: Laboratory of Ultrastructure Research, Aichi Cancer Center Research Institute, Chikusa-ku, Nagoya 464-8681, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Haruki
authors.forename: Y
authors.initials: Y
authors.lastname: Yatabe
authors.forename: W D
authors.initials: WD
authors.lastname: Travis
authors.forename: S
authors.initials: S
authors.lastname: Nomoto
authors.forename: H
authors.initials: H
authors.lastname: Osada
authors.forename: S
authors.initials: S
authors.lastname: Nakamura
authors.forename: A
authors.initials: A
authors.lastname: Nakao
authors.forename: Y
authors.initials: Y
authors.lastname: Fujii
authors.forename: T
authors.initials: T
authors.lastname: Takahashi
mesh_terms: D018287:Carcinoma, Large Cell / Q000235:genetics*; D018288:Carcinoma, Small Cell / Q000235:genetics*; D017931:DNA Primers; D016147:Genes, Tumor Suppressor / Q000235:genetics*; D005819:Genetic Markers; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D018761:Multiple Endocrine Neoplasia Type 1 / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D011518:Proto-Oncogene Proteins
chemical_list: D017931:DNA Primers; D005819:Genetic Markers; C105373:MEN1 protein, human; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins