{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T19:25:39Z","timestamp":1793042739536,"version":"4.5.0"},"reference-count":34,"publisher":"National Academy of Sciences","issue":"10","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2007,3,6]]},"abstract":"<jats:p>\n                    Pituitary adenomas are common neoplasms of the anterior pituitary gland. Germ-line mutations in the aryl hydrocarbon receptor-interacting protein (\n                    <jats:italic>AIP<\/jats:italic>\n                    ) gene cause pituitary adenoma predisposition (PAP), a recent discovery based on genetic studies in Northern Finland. In this population, a founder mutation explained a significant proportion of all acromegaly cases. Typically, PAP patients were of a young age at diagnosis but did not display a strong family history of pituitary adenomas. To evaluate the role of\n                    <jats:italic>AIP<\/jats:italic>\n                    in pituitary adenoma susceptibility in other populations and to gain insight into patient selection for molecular screening of the condition, we investigated the possible contribution of\n                    <jats:italic>AIP<\/jats:italic>\n                    mutations in pituitary tumorigenesis in patients from Europe and the United States. A total of 460 patients were investigated by\n                    <jats:italic>AIP<\/jats:italic>\n                    sequencing: young acromegaly patients, unselected acromegaly patients, unselected pituitary adenoma patients, and endocrine neoplasia-predisposition patients who were negative for\n                    <jats:italic>MEN1<\/jats:italic>\n                    mutations. Nine\n                    <jats:italic>AIP<\/jats:italic>\n                    mutations were identified. Because many of the patients displayed no family history of pituitary adenomas, detection of the condition appears challenging. Feasibility of AIP immunohistochemistry (IHC) as a prescreening tool was tested in 50 adenomas: 12\n                    <jats:italic>AIP<\/jats:italic>\n                    mutation-positive versus 38 mutation-negative pituitary tumors. AIP IHC staining levels proved to be a useful predictor of\n                    <jats:italic>AIP<\/jats:italic>\n                    status, with 75% sensitivity and 95% specificity for germ-line mutations.\n                    <jats:italic>AIP<\/jats:italic>\n                    contributes to PAP in all studied populations. AIP IHC, followed by genetic counseling and possible\n                    <jats:italic>AIP<\/jats:italic>\n                    mutation analysis in IHC-negative cases, a procedure similar to the diagnostics of the Lynch syndrome, appears feasible in identification of PAP.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0700004104","type":"journal-article","created":{"date-parts":[[2007,3,1]],"date-time":"2007-03-01T06:29:21Z","timestamp":1172730561000},"page":"4101-4105","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":149,"title":["Molecular diagnosis of pituitary adenoma predisposition caused by aryl hydrocarbon receptor-interacting protein gene mutations"],"prefix":"10.1073","volume":"104","author":[{"given":"Marianthi","family":"Georgitsi","sequence":"first","affiliation":[{"name":"Department of Medical Genetics, Molecular and Cancer Biology Research Program, University of Helsinki, P.O. Box 63, 00014, Helsinki, Finland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anniina","family":"Raitila","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Molecular and Cancer Biology Research Program, University of Helsinki, P.O. Box 63, 00014, Helsinki, Finland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Auli","family":"Karhu","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Molecular and Cancer Biology Research Program, University of Helsinki, P.O. Box 63, 00014, Helsinki, Finland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karoliina","family":"Tuppurainen","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Oulu, P.O. Box 5000, 90014, Oulu, Finland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus J.","family":"M\u00e4kinen","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Oulu, P.O. Box 5000, 90014, Oulu, Finland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Outi","family":"Vierimaa","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Oulu University Hospital, P.O. Box 60, 90029, Oulu, Finland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf","family":"Paschke","sequence":"additional","affiliation":[{"name":"Medical Department III, Leipzig University, Ph-Rosenthal-Street 27, 04103 Leipzig, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Saeger","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Marienkrankenhaus, Alfredstrasse 9, 22087 Hamburg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rob B.","family":"van der Luijt","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, University Medical Centre Utrecht, P.O. Box 85090, 3508 GA, Utrecht, The Netherlands;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timo","family":"Sane","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Helsinki University Central Hospital, P.O. Box 340, 00029, Helsinki, Finland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mercedes","family":"Robledo","sequence":"additional","affiliation":[{"name":"Hereditary Endocrine Cancer Group, Human Cancer Genetics Programme, Spanish National Cancer Center (CNIO), Melchor Fern\u00e1ndez Almagro 3, 28029 Madrid, Spain;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernesto","family":"De Menis","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, General Hospital, Piazza Ospedale 1, 31100 Treviso, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.","family":"Weil","sequence":"additional","affiliation":[{"name":"Brain Tumor Institute and Department of Neurosurgery, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Wasik","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Nencki Institute of Experimental Biology, Pasteura 3, 02093, Warsaw, Poland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grzegorz","family":"Zielinski","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Military Institute of the Health Services, Szaserow 128, 00909, Warsaw, Poland; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Lucewicz","sequence":"additional","affiliation":[{"name":"Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Polabska 4, 70115, Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Lubinski","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Nencki Institute of Experimental Biology, Pasteura 3, 02093, Warsaw, Poland;"},{"name":"Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Polabska 4, 70115, Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virpi","family":"Launonen","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Molecular and Cancer Biology Research Program, University of Helsinki, P.O. 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