Molecular diagnosis of pituitary adenoma predisposition caused by aryl hydrocarbon receptor-interacting protein gene mutations

Marianthi Georgitsi, Anniina Raitila, Auli Karhu, Karoliina Tuppurainen, Markus J Mäkinen, Outi Vierimaa, Ralf Paschke, Wolfgang Saeger, Rob B van der Luijt, Timo Sane, Mercedes Robledo, Ernesto de Menis, Robert J Weil, Anna Wasik, Grzegorz Zielinski, Olga Lucewicz, Jan Lubinski, Virpi Launonen, Pia Vahteristo, Lauri A Aaltonen

    Tutkimustuotos: ArtikkelijulkaisuArtikkeliTieteellinenvertaisarvioitu

    Kuvaus

    Pituitary adenomas are common neoplasms of the anterior pituitary gland. Germ-line mutations in the aryl hydrocarbon receptor-interacting protein (AIP) 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 AIP 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 AIP mutations in pituitary tumorigenesis in patients from Europe and the United States. A total of 460 patients were investigated by AIP sequencing: young acromegaly patients, unselected acromegaly patients, unselected pituitary adenoma patients, and endocrine neoplasia-predisposition patients who were negative for MEN1 mutations. Nine AIP 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 AM mutation-positive versus 38 mutation-negative pituitary tumors. AIP IHC staining levels proved to be a useful predictor of AIP status, with 75% sensitivity and 95% specificity for germ-line mutations. AIP contributes to PAP in all studied populations. AIP IHC, followed by genetic counseling and possible AIP mutation analysis in IHC-negative cases, a procedure similar to the diagnostics of the Lynch syndrome, appears feasible in identification of PAP.
    Alkuperäiskielienglanti
    LehtiProceedings of the National Academy of Sciences of the United States of America
    Vuosikerta104
    Sivut4101-4105
    Sivumäärä5
    ISSN0027-8424
    DOI - pysyväislinkit
    TilaJulkaistu - 2007
    OKM-julkaisutyyppiA1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä, vertaisarvioitu

    Tieteenalat

    • 311 Peruslääketieteet

    Lainaa tätä

    Georgitsi, Marianthi ; Raitila, Anniina ; Karhu, Auli ; Tuppurainen, Karoliina ; Mäkinen, Markus J ; Vierimaa, Outi ; Paschke, Ralf ; Saeger, Wolfgang ; van der Luijt, Rob B ; Sane, Timo ; Robledo, Mercedes ; de Menis, Ernesto ; Weil, Robert J ; Wasik, Anna ; Zielinski, Grzegorz ; Lucewicz, Olga ; Lubinski, Jan ; Launonen, Virpi ; Vahteristo, Pia ; Aaltonen, Lauri A. / Molecular diagnosis of pituitary adenoma predisposition caused by aryl hydrocarbon receptor-interacting protein gene mutations. Julkaisussa: Proceedings of the National Academy of Sciences of the United States of America. 2007 ; Vuosikerta 104. Sivut 4101-4105.
    @article{e4504f1a7fc64411a14069cad0c0a520,
    title = "Molecular diagnosis of pituitary adenoma predisposition caused by aryl hydrocarbon receptor-interacting protein gene mutations",
    abstract = "Pituitary adenomas are common neoplasms of the anterior pituitary gland. Germ-line mutations in the aryl hydrocarbon receptor-interacting protein (AIP) 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 AIP 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 AIP mutations in pituitary tumorigenesis in patients from Europe and the United States. A total of 460 patients were investigated by AIP sequencing: young acromegaly patients, unselected acromegaly patients, unselected pituitary adenoma patients, and endocrine neoplasia-predisposition patients who were negative for MEN1 mutations. Nine AIP 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 AM mutation-positive versus 38 mutation-negative pituitary tumors. AIP IHC staining levels proved to be a useful predictor of AIP status, with 75{\%} sensitivity and 95{\%} specificity for germ-line mutations. AIP contributes to PAP in all studied populations. AIP IHC, followed by genetic counseling and possible AIP mutation analysis in IHC-negative cases, a procedure similar to the diagnostics of the Lynch syndrome, appears feasible in identification of PAP.",
    keywords = "311 Basic medicine",
    author = "Marianthi Georgitsi and Anniina Raitila and Auli Karhu and Karoliina Tuppurainen and M{\"a}kinen, {Markus J} and Outi Vierimaa and Ralf Paschke and Wolfgang Saeger and {van der Luijt}, {Rob B} and Timo Sane and Mercedes Robledo and {de Menis}, Ernesto and Weil, {Robert J} and Anna Wasik and Grzegorz Zielinski and Olga Lucewicz and Jan Lubinski and Virpi Launonen and Pia Vahteristo and Aaltonen, {Lauri A}",
    year = "2007",
    doi = "10.1073/pnas.0700004104",
    language = "English",
    volume = "104",
    pages = "4101--4105",
    journal = "Proceedings of the National Academy of Sciences of the United States of America",
    issn = "0027-8424",
    publisher = "National Academy of Sciences",

    }

    Georgitsi, M, Raitila, A, Karhu, A, Tuppurainen, K, Mäkinen, MJ, Vierimaa, O, Paschke, R, Saeger, W, van der Luijt, RB, Sane, T, Robledo, M, de Menis, E, Weil, RJ, Wasik, A, Zielinski, G, Lucewicz, O, Lubinski, J, Launonen, V, Vahteristo, P & Aaltonen, LA 2007, 'Molecular diagnosis of pituitary adenoma predisposition caused by aryl hydrocarbon receptor-interacting protein gene mutations', Proceedings of the National Academy of Sciences of the United States of America, Vuosikerta 104, Sivut 4101-4105. https://doi.org/10.1073/pnas.0700004104

    Molecular diagnosis of pituitary adenoma predisposition caused by aryl hydrocarbon receptor-interacting protein gene mutations. / Georgitsi, Marianthi; Raitila, Anniina; Karhu, Auli; Tuppurainen, Karoliina; Mäkinen, Markus J; Vierimaa, Outi; Paschke, Ralf; Saeger, Wolfgang; van der Luijt, Rob B; Sane, Timo; Robledo, Mercedes; de Menis, Ernesto; Weil, Robert J; Wasik, Anna; Zielinski, Grzegorz; Lucewicz, Olga; Lubinski, Jan; Launonen, Virpi; Vahteristo, Pia; Aaltonen, Lauri A.

    julkaisussa: Proceedings of the National Academy of Sciences of the United States of America, Vuosikerta 104, 2007, s. 4101-4105.

    Tutkimustuotos: ArtikkelijulkaisuArtikkeliTieteellinenvertaisarvioitu

    TY - JOUR

    T1 - Molecular diagnosis of pituitary adenoma predisposition caused by aryl hydrocarbon receptor-interacting protein gene mutations

    AU - Georgitsi, Marianthi

    AU - Raitila, Anniina

    AU - Karhu, Auli

    AU - Tuppurainen, Karoliina

    AU - Mäkinen, Markus J

    AU - Vierimaa, Outi

    AU - Paschke, Ralf

    AU - Saeger, Wolfgang

    AU - van der Luijt, Rob B

    AU - Sane, Timo

    AU - Robledo, Mercedes

    AU - de Menis, Ernesto

    AU - Weil, Robert J

    AU - Wasik, Anna

    AU - Zielinski, Grzegorz

    AU - Lucewicz, Olga

    AU - Lubinski, Jan

    AU - Launonen, Virpi

    AU - Vahteristo, Pia

    AU - Aaltonen, Lauri A

    PY - 2007

    Y1 - 2007

    N2 - Pituitary adenomas are common neoplasms of the anterior pituitary gland. Germ-line mutations in the aryl hydrocarbon receptor-interacting protein (AIP) 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 AIP 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 AIP mutations in pituitary tumorigenesis in patients from Europe and the United States. A total of 460 patients were investigated by AIP sequencing: young acromegaly patients, unselected acromegaly patients, unselected pituitary adenoma patients, and endocrine neoplasia-predisposition patients who were negative for MEN1 mutations. Nine AIP 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 AM mutation-positive versus 38 mutation-negative pituitary tumors. AIP IHC staining levels proved to be a useful predictor of AIP status, with 75% sensitivity and 95% specificity for germ-line mutations. AIP contributes to PAP in all studied populations. AIP IHC, followed by genetic counseling and possible AIP mutation analysis in IHC-negative cases, a procedure similar to the diagnostics of the Lynch syndrome, appears feasible in identification of PAP.

    AB - Pituitary adenomas are common neoplasms of the anterior pituitary gland. Germ-line mutations in the aryl hydrocarbon receptor-interacting protein (AIP) 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 AIP 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 AIP mutations in pituitary tumorigenesis in patients from Europe and the United States. A total of 460 patients were investigated by AIP sequencing: young acromegaly patients, unselected acromegaly patients, unselected pituitary adenoma patients, and endocrine neoplasia-predisposition patients who were negative for MEN1 mutations. Nine AIP 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 AM mutation-positive versus 38 mutation-negative pituitary tumors. AIP IHC staining levels proved to be a useful predictor of AIP status, with 75% sensitivity and 95% specificity for germ-line mutations. AIP contributes to PAP in all studied populations. AIP IHC, followed by genetic counseling and possible AIP mutation analysis in IHC-negative cases, a procedure similar to the diagnostics of the Lynch syndrome, appears feasible in identification of PAP.

    KW - 311 Basic medicine

    U2 - 10.1073/pnas.0700004104

    DO - 10.1073/pnas.0700004104

    M3 - Article

    VL - 104

    SP - 4101

    EP - 4105

    JO - Proceedings of the National Academy of Sciences of the United States of America

    JF - Proceedings of the National Academy of Sciences of the United States of America

    SN - 0027-8424

    ER -