{"doi":"10.1111/j.1365-2265.2008.03487.x","title":"Low O\n                    <sup>6</sup>\n                    ‐methylguanine‐DNA methyltransferase (MGMT) expression and response to temozolomide in aggressive pituitary tumours","abstract":"<jats:title>Summary</jats:title>\n                  <jats:p>\n                    <jats:bold>Context </jats:bold>\n                    Recent case reports detail the successful use of temozolomide in the management of aggressive pituitary tumours. O\n                    <jats:sup>6</jats:sup>\n                    ‐methylguanine‐DNA methyltransferase (MGMT) is a DNA repair protein that counteracts the effect of temozolomide.\n                  </jats:p>\n                  <jats:p>\n                    <jats:bold>Objective </jats:bold>\n                    To study MGMT expression in pituitary tumours and consider whether MGMT expression is associated with response to temozolomide therapy in aggressive pituitary tumours.\n                  </jats:p>\n                  <jats:p>\n                    <jats:bold>Patients </jats:bold>\n                    We report two patients with aggressive pituitary tumours treated with temozolomide, one who responded to temozolomide and the other who did not. MGMT expression was assessed in a further 88 archived pituitary tumour samples.\n                  </jats:p>\n                  <jats:p>\n                    <jats:bold>Design </jats:bold>\n                    MGMT expression was assessed by immunohistochemistry.\n                    <jats:italic>MGMT</jats:italic>\n                    promoter methylation was studied by methylation‐specific polymerase chain reaction (MSP), sequencing of\n                    <jats:italic>MGMT</jats:italic>\n                    was performed and loss of heterozygosity (LOH) analysis undertaken.\n                  </jats:p>\n                  <jats:p>\n                    <jats:bold>Results </jats:bold>\n                    Low MGMT expression and\n                    <jats:italic>MGMT</jats:italic>\n                    promoter methylation were found in the pituitary tumour of the patient who responded to temozolomide. Conversely, high MGMT expression was seen in the patient demonstrating a poor response to temozolomide. Eleven out of 88 archived tumour samples (13%) had low MGMT expression. Prolactinomas were more likely to have low MGMT expression compared with other pituitary tumour subtypes (\n                    <jats:italic>P &lt;</jats:italic>\n                     0·001). There was no significant difference in MGMT expression between invasive and noninvasive tumours, or between recurrent and nonrecurrent tumours. A significant inverse correlation was found between MGMT expression and promoter methylation (\n                    <jats:italic>P =</jats:italic>\n                     0·012).\n                  </jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusion </jats:bold>\n                    MGMT expression as assessed by immunohistochemistry may predict response to temozolomide therapy in patients with aggressive pituitary tumours.\n                    <jats:italic>MGMT</jats:italic>\n                    promoter methylation is likely to explain low MGMT expression in some, but not all, pituitary tumours.\n                  </jats:p>","journal":"Clinical Endocrinology","year":2009,"id":635408,"datarank":0.7390880527735809,"base_score":4.927253685157205,"endowment":4.927253685157205,"self_citation_contribution":0.7390880527735809,"citation_network_contribution":0.0,"self_endowment_contribution":0.7390880527735809,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":137,"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":1648509,"name":"Kerrie L. McDonald","orcid":null,"position":1,"is_corresponding":false},{"id":13489,"name":"Anthony J. Gill","orcid":"0000-0002-9447-1967","position":2,"is_corresponding":false},{"id":1237550,"name":"Susan J. Clark","orcid":"0000-0001-5925-5030","position":3,"is_corresponding":false},{"id":1648512,"name":"Morton G. Burt","orcid":null,"position":4,"is_corresponding":false},{"id":1648514,"name":"Kirsten A. Campbell","orcid":null,"position":5,"is_corresponding":false},{"id":1648515,"name":"Wilton J. Braund","orcid":null,"position":6,"is_corresponding":false},{"id":1648516,"name":"Nicholas S. Little","orcid":null,"position":7,"is_corresponding":false},{"id":1648518,"name":"Raymond J. Cook","orcid":null,"position":8,"is_corresponding":false},{"id":121577,"name":"Ashley B. Grossman","orcid":null,"position":9,"is_corresponding":false},{"id":1523255,"name":"Bruce G. Robinson","orcid":null,"position":10,"is_corresponding":false},{"id":1648520,"name":"Roderick J. Clifton‐Bligh","orcid":null,"position":11,"is_corresponding":false},{"id":1648504,"name":"Ann I. McCormack","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Low O\n                    <sup>6</sup>\n                    ‐methylguanine‐DNA methyltransferase (MGMT) expression and response to temozolomide in aggressive pituitary tumours","abstract":"<jats:title>Summary</jats:title>\n                  <jats:p>\n                    <jats:bold>Context </jats:bold>\n                    Recent case reports detail the successful use of temozolomide in the management of aggressive pituitary tumours. O\n                    <jats:sup>6</jats:sup>\n                    ‐methylguanine‐DNA methyltransferase (MGMT) is a DNA repair protein that counteracts the effect of temozolomide.\n                  </jats:p>\n                  <jats:p>\n                    <jats:bold>Objective </jats:bold>\n                    To study MGMT expression in pituitary tumours and consider whether MGMT expression is associated with response to temozolomide therapy in aggressive pituitary tumours.\n                  </jats:p>\n                  <jats:p>\n                    <jats:bold>Patients </jats:bold>\n                    We report two patients with aggressive pituitary tumours treated with temozolomide, one who responded to temozolomide and the other who did not. MGMT expression was assessed in a further 88 archived pituitary tumour samples.\n                  </jats:p>\n                  <jats:p>\n                    <jats:bold>Design </jats:bold>\n                    MGMT expression was assessed by immunohistochemistry.\n                    <jats:italic>MGMT</jats:italic>\n                    promoter methylation was studied by methylation‐specific polymerase chain reaction (MSP), sequencing of\n                    <jats:italic>MGMT</jats:italic>\n                    was performed and loss of heterozygosity (LOH) analysis undertaken.\n                  </jats:p>\n                  <jats:p>\n                    <jats:bold>Results </jats:bold>\n                    Low MGMT expression and\n                    <jats:italic>MGMT</jats:italic>\n                    promoter methylation were found in the pituitary tumour of the patient who responded to temozolomide. Conversely, high MGMT expression was seen in the patient demonstrating a poor response to temozolomide. Eleven out of 88 archived tumour samples (13%) had low MGMT expression. Prolactinomas were more likely to have low MGMT expression compared with other pituitary tumour subtypes (\n                    <jats:italic>P &lt;</jats:italic>\n                     0·001). There was no significant difference in MGMT expression between invasive and noninvasive tumours, or between recurrent and nonrecurrent tumours. A significant inverse correlation was found between MGMT expression and promoter methylation (\n                    <jats:italic>P =</jats:italic>\n                     0·012).\n                  </jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusion </jats:bold>\n                    MGMT expression as assessed by immunohistochemistry may predict response to temozolomide therapy in patients with aggressive pituitary tumours.\n                    <jats:italic>MGMT</jats:italic>\n                    promoter methylation is likely to explain low MGMT expression in some, but not all, pituitary tumours.\n                  </jats:p>","is_dataset_classified":null,"base_score":4.927253685157205,"endowment":4.927253685157205,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"19067722","pmcid":null,"openalex_id":"https://openalex.org/W2063431624","authors":[],"funders":[],"total_grants":0,"fwci":5.149,"citation_percentile":0.95872906,"influential_citations":0,"citation_trend":[{"year":2012,"count":14},{"year":2013,"count":13},{"year":2014,"count":10},{"year":2015,"count":11},{"year":2016,"count":10},{"year":2017,"count":9},{"year":2018,"count":2},{"year":2019,"count":4},{"year":2020,"count":3},{"year":2021,"count":4},{"year":2022,"count":4},{"year":2023,"count":5},{"year":2024,"count":1},{"year":2025,"count":7},{"year":2026,"count":4}],"oa_status":"closed","license":"http://onlinelibrary.wiley.com/termsAndConditions#vor","oa_locations":[{"url":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1111%2Fj.1365-2265.2008.03487.x","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1365-2265.2008.03487.x","host_type":"publisher"},{"url":"https://doi.org/10.1111/j.1365-2265.2008.03487.x","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/19067722","host_type":"repository"},{"url":"http://hdl.handle.net/2328/32408","host_type":"repository"}],"fields_of_study":["Glioma Diagnosis and Treatment","Pituitary Gland Disorders and Treatments","Chromatin Remodeling and Cancer","Adult","Cohort Studies","Dacarbazine","Gene Expression","Humans","Male","Middle Aged","O(6)-Methylguanine-DNA Methyltransferase","Pituitary Neoplasms","Temozolomide"],"mesh_terms":["Temozolomide","Adult","Dacarbazine","Humans","Male","Middle Aged","Pituitary Neoplasms","Cohort Studies","Gene Expression","O(6)-Methylguanine-DNA Methyltransferase"],"keywords":["Temozolomide","Methyltransferase","O-6-methylguanine-DNA methyltransferase","Immunohistochemistry","DNA methyltransferase","Methylation","Cancer research","DNA methylation","Pituitary neoplasm","Internal medicine","Medicine","Biology","Oncology","Chemotherapy","Gene expression","Pituitary gland","DNA","Genetics","Gene"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-06T15:03:07.840593Z","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":[]}