Anna Wasik

Publications (2)12.85 Total impact

• Article: Aryl hydrocarbon receptor interacting protein (AIP) gene mutation analysis in children and adolescents with sporadic pituitary adenomas

  Marianthi Georgitsi, Ernesto De Menis, Salvatore Cannavò, Markus J. Mäkinen, Karoliina Tuppurainen, Paolo Pauletto, Lorenzo Curtò, Robert J. Weil, Ralf Paschke, Grzegorz Zielinski, Anna Wasik, Jan Lubinski, Pia Vahteristo, Auli Karhu, Lauri A. Aaltonen
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  ABSTRACT: Objective Pituitary adenomas occur rarely in childhood and adolescence. Pituitary adenoma predisposition (PAP) has been recently associated with germline mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene. The aim of the study was to examine the proportion of germline AIP mutations in apparently sporadic paediatric pituitary adenomas.Design Genomic DNA was analysed for mutations in the AIP gene, by PCR amplification and direct sequencing.Patients A population-based cohort consisting of 36 apparently sporadic paediatric pituitary adenoma patients, referred to two medical centres in Italy, was included in the study. Patients were either less than 18 years at diagnosis, or showed clinical evidence of adenoma development before the age of 18 years.Results A heterozygous in-frame deletion Y248del (c.742_744delTAC) was identified in one GH-secreting adenoma patient. Loss of heterozygosity (LOH) analysis of tumour DNA revealed the loss of the wild-type allele. First degree relatives carrying the mutation were clinically unaffected.Conclusions While mutations were absent in non-GH-secreting adenoma patients, germline AIP mutations can be found in children and adolescents with GH-secreting tumours, even in the absence of family history. The present study reports the AIP mutation analysis results on patients of a single ethnic origin. Clearly, further studies are needed to improve our knowledge on the role of AIP in paediatric pituitary adenomas.
  Clinical Endocrinology 04/2008; 69(4):621 - 627. · 3.17 Impact Factor
• Source

  Available from: Karoliina Stefanius

  Article: 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
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  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 AIP 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.
  Proceedings of the National Academy of Sciences 04/2007; 104(10):4101-5. · 9.68 Impact Factor