{"doi":"10.1073/pnas.97.11.6085","title":"Mutations in the tuberous sclerosis complex gene\n                    <i>TSC2</i>\n                    are a cause of sporadic pulmonary lymphangioleiomyomatosis","abstract":"<jats:p>\n                    Lymphangioleiomyomatosis (LAM) is a progressive and often fatal interstitial lung disease characterized by a diffuse proliferation of abnormal smooth muscle cells in the lungs. LAM is of unusual interest biologically because it affects almost exclusively young women. LAM can occur as an isolated disorder (sporadic LAM) or in association with tuberous sclerosis complex. Renal angiomyolipomas, which are found in most tuberous sclerosis patients, also occur in 60% of sporadic LAM patients. We previously found\n                    <jats:italic>TSC2</jats:italic>\n                    loss of heterozygosity in 7 of 13 (54%) of angiomyolipomas from sporadic LAM patients, suggesting that LAM and TSC could have a common genetic basis. In this study, we report the identification of somatic\n                    <jats:italic>TSC2</jats:italic>\n                    mutations in five of seven angiomyolipomas from sporadic LAM patients. In all four patients from whom lung tissue was available, the same mutation found in the angiomyolipoma was present in the abnormal pulmonary smooth muscle cells. In no case was the mutation present in normal kidney, morphologically normal lung, or lymphoblastoid cells. Our data demonstrate that somatic mutations in the\n                    <jats:italic>TSC2</jats:italic>\n                    gene occur in the angiomyolipomas and pulmonary LAM cells of women with sporadic LAM, strongly supporting a direct role of\n                    <jats:italic>TSC2</jats:italic>\n                    in the pathogenesis of this disease.\n                  </jats:p>","journal":"Proceedings of the National Academy of Sciences","year":2000,"id":650655,"datarank":0.9713149075056137,"base_score":6.47543271670409,"endowment":6.47543271670409,"self_citation_contribution":0.9713149075056137,"citation_network_contribution":0.0,"self_endowment_contribution":0.9713149075056137,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":648,"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":1010687,"name":"Aristotelis Astrinidis","orcid":"0000-0001-7098-1391","position":1,"is_corresponding":false},{"id":1696594,"name":"Elizabeth Petri Henske","orcid":null,"position":2,"is_corresponding":false},{"id":1696592,"name":"Thomas Carsillo","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Mutations in the tuberous sclerosis complex gene <i>TSC2</i> are a cause of sporadic pulmonary lymphangioleiomyomatosis","abstract":"Lymphangioleiomyomatosis (LAM) is a progressive and often fatal interstitial lung disease characterized by a diffuse proliferation of abnormal smooth muscle cells in the lungs. LAM is of unusual interest biologically because it affects almost exclusively young women. LAM can occur as an isolated disorder (sporadic LAM) or in association with tuberous sclerosis complex. Renal angiomyolipomas, which are found in most tuberous sclerosis patients, also occur in 60% of sporadic LAM patients. We previously found TSC2 loss of heterozygosity in 7 of 13 (54%) of angiomyolipomas from sporadic LAM patients, suggesting that LAM and TSC could have a common genetic basis. In this study, we report the identification of somatic TSC2 mutations in five of seven angiomyolipomas from sporadic LAM patients. In all four patients from whom lung tissue was available, the same mutation found in the angiomyolipoma was present in the abnormal pulmonary smooth muscle cells. In no case was the mutation present in normal kidney, morphologically normal lung, or lymphoblastoid cells. Our data demonstrate that somatic mutations in the TSC2 gene occur in the angiomyolipomas and pulmonary LAM cells of women with sporadic LAM, strongly supporting a direct role of TSC2 in the pathogenesis of this disease.","is_dataset_classified":null,"base_score":6.47543271670409,"endowment":6.47543271670409,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"10823953","pmcid":"PMC18562","openalex_id":"https://openalex.org/W2038028072","authors":[],"funders":[{"funder_name":"NHLBI NIH HHS","grant_id":"R01 HL 60746","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"R01 HL060746","title":null},{"funder_name":"National Institutes of Health","grant_id":"1R01HL060746-01A1","title":"MOLECULAR BASIS OF LYMPHANGIOMYOMATOSIS"}],"total_grants":3,"fwci":10.5026,"citation_percentile":0.98922659,"influential_citations":0,"citation_trend":[{"year":2012,"count":23},{"year":2013,"count":26},{"year":2014,"count":32},{"year":2015,"count":31},{"year":2016,"count":33},{"year":2017,"count":27},{"year":2018,"count":24},{"year":2019,"count":28},{"year":2020,"count":28},{"year":2021,"count":35},{"year":2022,"count":28},{"year":2023,"count":21},{"year":2024,"count":19},{"year":2025,"count":16},{"year":2026,"count":7}],"oa_status":"green","license":null,"oa_locations":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/18562","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/18562","host_type":"repository"},{"url":"https://doi.org/10.1073/pnas.97.11.6085","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/10823953","host_type":"repository"},{"url":"http://www.pnas.org/content/97/11/6085.full.pdf","host_type":""},{"url":"https://dx.doi.org/10.1073/pnas.97.11.6085","host_type":""}],"fields_of_study":["Tuberous Sclerosis Complex Research","0301 basic medicine","03 medical and health sciences","0302 clinical medicine"],"mesh_terms":["Tuberous Sclerosis Complex 2 Protein","Adult","Cell Transformation, Neoplastic","DNA Mutational Analysis","DNA, Neoplasm","Female","Genotype","Humans","Kidney","Lung Neoplasms","Muscle, Smooth","Neoplastic Syndromes, Hereditary","Repressor Proteins","Tuberous Sclerosis","Point Mutation","Sequence Deletion","Lymphangioleiomyomatosis","Genetic Predisposition to Disease","Tumor Suppressor Proteins"],"keywords":["Tuberous sclerosis","Lymphangioleiomyomatosis","TSC2","Angiomyolipoma","TSC1","Loss of heterozygosity","Pathology","Pathogenesis","Lung","Mutation","Medicine","Germline mutation","Compound heterozygosity","Biology","Kidney","Gene","Internal medicine","Allele","Genetics","Adult","Lung Neoplasms","Genotype","Tumor Suppressor Proteins","DNA Mutational Analysis","Muscle, Smooth","DNA, Neoplasm","Repressor Proteins","Cell Transformation, Neoplastic","Neoplastic Syndromes, Hereditary","Tuberous Sclerosis Complex 2 Protein","Humans","Point Mutation","Female","Genetic Predisposition to Disease","Sequence Deletion"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. 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