{"doi":"10.1530/erc-21-0226","title":"Two distinct classes of thymic tumors in patients with MEN1 show LOH at the MEN1 locus","abstract":"Patients with the multiple endocrine neoplasia type 1 (MEN1) syndrome carry germline heterozygous loss-of-function mutations in the MEN1 gene which predisposes them to develop various endocrine and non-endocrine tumors. Over 90% of the tumors show loss of heterozygosity (LOH) at chromosome 11q13, the MEN1 locus, due to somatic loss of the wild-type MEN1 allele. Thymic neuroendocrine tumors (NETs) or thymic carcinoids are uncommon in MEN1 patients but are a major cause of mortality. LOH at the MEN1 locus has not been demonstrated in thymic tumors. The goal of this study was to investigate the molecular aspects of MEN1-associated thymic tumors including LOH at the MEN1 locus and RNA-sequencing (RNA-Seq) to identify genes associated with tumor development and potential targeted therapy. A retrospective chart review of 294 patients with MEN1 germline mutations identified 14 patients (4.8%) with thymic tumors (12 thymic NETs and 2 thymomas). LOH at the MEN1 locus was identified in 10 tumors including the 2 thymomas, demonstrating that somatic LOH at the MEN1 locus is also the mechanism for thymic tumor development. Unsupervised principal component analysis and hierarchical clustering of RNA-Seq data showed that thymic NETs formed a homogenous transcriptomic group separate from thymoma and normal thymus. KSR2 (kinase suppressor of Ras 2), that promotes Ras-mediated signaling, was abundantly expressed in thymic NETs, a potential therapeutic target. The molecular insights gained from our study about thymic tumors combined with similar data from other MEN1-associated tumors may lead to better surveillance and treatment of these rare tumors.","journal":"Endocrine Related Cancer","year":2021,"id":181465,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"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":0.9492,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":207666,"name":"James Welch","orcid":null,"position":1,"is_corresponding":false},{"id":733118,"name":"Gayathri Kapoor","orcid":null,"position":2,"is_corresponding":false},{"id":733119,"name":"Vaishali I. Parekh","orcid":null,"position":3,"is_corresponding":false},{"id":399102,"name":"David S. Schrump","orcid":"0000-0003-3613-1400","position":4,"is_corresponding":false},{"id":5682,"name":"R. Taylor Ripley","orcid":"0000-0003-0053-307X","position":5,"is_corresponding":false},{"id":234133,"name":"Mary Walter","orcid":null,"position":6,"is_corresponding":false},{"id":302291,"name":"Jaydira Del Rivero","orcid":"0000-0001-9710-4030","position":7,"is_corresponding":false},{"id":331658,"name":"Smita Jha","orcid":"0000-0001-9201-3340","position":8,"is_corresponding":false},{"id":331822,"name":"William F. Simonds","orcid":"0000-0001-7806-706X","position":9,"is_corresponding":false},{"id":404129,"name":"Robert T. Jensen","orcid":"0000-0002-0095-4600","position":10,"is_corresponding":false},{"id":292018,"name":"Lee S. Weinstein","orcid":"0000-0002-1899-5152","position":11,"is_corresponding":false},{"id":339670,"name":"Jenny E. Blau","orcid":"0000-0002-6725-4262","position":12,"is_corresponding":false},{"id":245220,"name":"Sunita Agarwal","orcid":"0000-0002-7557-3191","position":13,"is_corresponding":false},{"id":436145,"name":"Adel Mandl","orcid":"0000-0002-2852-7280","position":0,"is_corresponding":true}],"reference_count":10,"raw_metadata":null,"created_at":"2026-07-18T23:48:05.146883Z","pmid":"34515662","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":[]}