{"doi":"10.1111/j.1349-7006.2000.tb00947.x","title":"Characterization of High‐grade Neuroendocrine Tumors of the Lung in Relation to menin Mutations","abstract":"<jats:p>It has been suggested that mutations in the <jats:italic>menin</jats:italic> gene play a role in the development of multiple endocrine neoplasia type 1 (MEN1)‐associated and of sporadic forms of low‐ and intermediategrade 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 <jats:italic>menin</jats:italic> 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 <jats:italic>menin</jats:italic> gene were not detected in any of the high‐grade neuroendocrine tumors examined. We thus conclude that <jats:italic>menin</jats:italic> 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 <jats:italic>menin</jats:italic> gene appeared to be more prevalent in LCNEC (50%) than in SCLC (22%), suggesting a possible distinction between SCLC and LCNEC.</jats:p>","journal":"Japanese Journal of Cancer Research","year":2000,"id":610544,"datarank":0.42498200160843247,"base_score":2.833213344056216,"endowment":2.833213344056216,"self_citation_contribution":0.42498200160843247,"citation_network_contribution":0.0,"self_endowment_contribution":0.42498200160843247,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":16,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":32032,"name":"Yasushi Yatabe","orcid":"0000-0003-1788-559X","position":1,"is_corresponding":false},{"id":15536,"name":"William D. Travis","orcid":"0000-0003-3160-6729","position":2,"is_corresponding":false},{"id":1569797,"name":"Shuji Nomoto","orcid":null,"position":3,"is_corresponding":false},{"id":32030,"name":"Hirotaka Osada","orcid":null,"position":4,"is_corresponding":false},{"id":202750,"name":"Shigeo Nakamura","orcid":null,"position":5,"is_corresponding":false},{"id":1569798,"name":"Akimasa Nakao","orcid":null,"position":6,"is_corresponding":false},{"id":86335,"name":"Yoshitaka Fujii","orcid":"0000-0003-2207-4230","position":7,"is_corresponding":false},{"id":428944,"name":"Takashi Takahashi","orcid":"0000-0002-3323-7069","position":8,"is_corresponding":false},{"id":1569796,"name":"Nobuhiro Haruki","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Characterization of High‐grade Neuroendocrine Tumors of the Lung in Relation to menin Mutations","abstract":"<jats:p>It has been suggested that mutations in the <jats:italic>menin</jats:italic> gene play a role in the development of multiple endocrine neoplasia type 1 (MEN1)‐associated and of sporadic forms of low‐ and intermediategrade 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 <jats:italic>menin</jats:italic> 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 <jats:italic>menin</jats:italic> gene were not detected in any of the high‐grade neuroendocrine tumors examined. We thus conclude that <jats:italic>menin</jats:italic> 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 <jats:italic>menin</jats:italic> gene appeared to be more prevalent in LCNEC (50%) than in SCLC (22%), suggesting a possible distinction between SCLC and LCNEC.</jats:p>","is_dataset_classified":null,"base_score":2.833213344056216,"endowment":2.833213344056216,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"10760691","pmcid":"PMC5926365","openalex_id":"https://openalex.org/W2060165156","authors":[],"funders":[],"total_grants":0,"fwci":1.4638,"citation_percentile":0.8200617,"influential_citations":0,"citation_trend":[{"year":2012,"count":1},{"year":2013,"count":2},{"year":2014,"count":1},{"year":2024,"count":1}],"oa_status":"green","license":"http://onlinelibrary.wiley.com/termsAndConditions#vor","oa_locations":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/5926365","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/5926365","host_type":"repository"},{"url":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1111%2Fj.1349-7006.2000.tb00947.x","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1349-7006.2000.tb00947.x","host_type":"publisher"},{"url":"https://doi.org/10.1111/j.1349-7006.2000.tb00947.x","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/10760691","host_type":"repository"},{"url":"http://europepmc.org/pmc/articles/PMC5926365","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC5926365","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC5926365?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Neuroendocrine Tumor Research Advances","Lung Cancer Research Studies","Lung Cancer Treatments and Mutations"],"mesh_terms":["Genetic Markers","Humans","Lung Neoplasms","Neoplasm Proteins","Proto-Oncogene Proteins","Genes, Tumor Suppressor","DNA Primers","Carcinoma, Large Cell","Carcinoma, Small Cell","Multiple Endocrine Neoplasia Type 1"],"keywords":["MEN1","Neuroendocrine tumors","Loss of heterozygosity","Multiple endocrine neoplasia","Cancer research","Biology","Mutation","Pathology","Neuroendocrine cell","Small Cell Lung Carcinoma","Gene mutation","Lung cancer","Gene","Medicine","Immunohistochemistry","Small-cell carcinoma","Endocrinology","Genetics","Allele"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-31T23:20:43.630608Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}