Large genomic deletions in AIP in pituitary adenoma predisposition

Marianthi Georgitsi; Elina Heliövaara; Ralf Paschke; Ajith V K Kumar; Marc Tischkowitz; Outi Vierimaa; Pasi Salmela; Timo Sane; Ernesto De Menis; Salvatore Cannavò; Sadi Gündogdu; Anneke Lucassen; Louise Izatt; Simon Aylwin; Gul Bano; Shirley Hodgson; Christian A Koch; Auli Karhu; Lauri A Aaltonen

doi:10.1210/jc.2008-1003

Large genomic deletions in AIP in pituitary adenoma predisposition

Marianthi Georgitsi, Elina Heliövaara, Ralf Paschke, Ajith V K Kumar, Marc Tischkowitz, Outi Vierimaa, Pasi Salmela, Timo Sane, Ernesto De Menis, Salvatore Cannavò, Sadi Gündogdu, Anneke Lucassen, Louise Izatt, Simon Aylwin, Gul Bano, Shirley Hodgson, Christian A Koch, Auli Karhu, Lauri A Aaltonen

Department of Medical Genetics, Biomedicum Helsinki, University of Helsinki, 00014 Helsinki, Finland.

Research output: Contribution to journal › Article › peer-review

75 Citations (Scopus)

Abstract

CONTEXT: Germline mutations in AIP have been recently shown to cause pituitary adenoma predisposition (PAP). Subsequently, many intragenic germline mutations have been reported, both in familial and in sporadic settings.

OBJECTIVE: Our objective was to evaluate the possible contribution of large genomic germline AIP deletions, an important mutation type in tumor predisposition syndromes, in PAP.

DESIGN: Here, we applied the multiplex ligation-dependent probe amplification assay to examine whether large genomic AIP or MEN1 alterations account for a subset of PAP cases.

PATIENTS: The study was performed on familial and sporadic pituitary adenoma cases of European origin, which had previously tested negative for germline AIP and MEN1 mutations by sequencing.

RESULTS: Two of 21 pituitary adenoma families (9.5%) were found to harbor an AIP deletion. No copy number changes were detected among 67 sporadic pituitary adenoma patients. No MEN1 deletions were found.

CONCLUSIONS: The present study shows that large genomic AIP deletions account for a subset of PAP. Therefore, in suspected PAP cases undergoing counseling and AIP genetic testing, multiplex ligation-dependent probe amplification could be considered if direct sequencing does not identify a mutation.

Original language	English
Pages (from-to)	4146-51
Number of pages	6
Journal	Journal of Clinical Endocrinology and Metabolism
Volume	93
Issue number	10
DOIs	https://doi.org/10.1210/jc.2008-1003
Publication status	Published - Oct 2008

Keywords

Adenoma/genetics
Adolescent
Adult
Base Sequence
DNA Mutational Analysis
Family
Female
Gene Deletion
Genetic Predisposition to Disease
Germ-Line Mutation
Humans
Intracellular Signaling Peptides and Proteins/genetics
Male
Middle Aged
Molecular Sequence Data
Pituitary Neoplasms/genetics
Precancerous Conditions/genetics

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10.1210/jc.2008-1003

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Georgitsi, M., Heliövaara, E., Paschke, R., Kumar, A. V. K., Tischkowitz, M., Vierimaa, O., Salmela, P., Sane, T., De Menis, E., Cannavò, S., Gündogdu, S., Lucassen, A., Izatt, L., Aylwin, S., Bano, G., Hodgson, S., Koch, C. A., Karhu, A., & Aaltonen, L. A. (2008). Large genomic deletions in AIP in pituitary adenoma predisposition. Journal of Clinical Endocrinology and Metabolism, 93(10), 4146-51. https://doi.org/10.1210/jc.2008-1003

@article{ef0c9f21104e4fb6a4bfde907fee97f3,

title = "Large genomic deletions in AIP in pituitary adenoma predisposition",

abstract = "CONTEXT: Germline mutations in AIP have been recently shown to cause pituitary adenoma predisposition (PAP). Subsequently, many intragenic germline mutations have been reported, both in familial and in sporadic settings.OBJECTIVE: Our objective was to evaluate the possible contribution of large genomic germline AIP deletions, an important mutation type in tumor predisposition syndromes, in PAP.DESIGN: Here, we applied the multiplex ligation-dependent probe amplification assay to examine whether large genomic AIP or MEN1 alterations account for a subset of PAP cases.PATIENTS: The study was performed on familial and sporadic pituitary adenoma cases of European origin, which had previously tested negative for germline AIP and MEN1 mutations by sequencing.RESULTS: Two of 21 pituitary adenoma families (9.5%) were found to harbor an AIP deletion. No copy number changes were detected among 67 sporadic pituitary adenoma patients. No MEN1 deletions were found.CONCLUSIONS: The present study shows that large genomic AIP deletions account for a subset of PAP. Therefore, in suspected PAP cases undergoing counseling and AIP genetic testing, multiplex ligation-dependent probe amplification could be considered if direct sequencing does not identify a mutation.",

keywords = "Adenoma/genetics, Adolescent, Adult, Base Sequence, DNA Mutational Analysis, Family, Female, Gene Deletion, Genetic Predisposition to Disease, Germ-Line Mutation, Humans, Intracellular Signaling Peptides and Proteins/genetics, Male, Middle Aged, Molecular Sequence Data, Pituitary Neoplasms/genetics, Precancerous Conditions/genetics",

author = "Marianthi Georgitsi and Elina Heli{\"o}vaara and Ralf Paschke and Kumar, {Ajith V K} and Marc Tischkowitz and Outi Vierimaa and Pasi Salmela and Timo Sane and {De Menis}, Ernesto and Salvatore Cannav{\`o} and Sadi G{\"u}ndogdu and Anneke Lucassen and Louise Izatt and Simon Aylwin and Gul Bano and Shirley Hodgson and Koch, {Christian A} and Auli Karhu and Aaltonen, {Lauri A}",

year = "2008",

month = oct,

doi = "10.1210/jc.2008-1003",

language = "English",

volume = "93",

pages = "4146--51",

journal = "Journal of Clinical Endocrinology and Metabolism",

issn = "0021-972X",

publisher = "Endocrine Society",

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Georgitsi, M, Heliövaara, E, Paschke, R, Kumar, AVK, Tischkowitz, M, Vierimaa, O, Salmela, P, Sane, T, De Menis, E, Cannavò, S, Gündogdu, S, Lucassen, A, Izatt, L , Aylwin, S, Bano, G, Hodgson, S, Koch, CA, Karhu, A & Aaltonen, LA 2008, 'Large genomic deletions in AIP in pituitary adenoma predisposition', Journal of Clinical Endocrinology and Metabolism, vol. 93, no. 10, pp. 4146-51. https://doi.org/10.1210/jc.2008-1003

TY - JOUR

T1 - Large genomic deletions in AIP in pituitary adenoma predisposition

AU - Georgitsi, Marianthi

AU - Heliövaara, Elina

AU - Paschke, Ralf

AU - Kumar, Ajith V K

AU - Tischkowitz, Marc

AU - Vierimaa, Outi

AU - Salmela, Pasi

AU - Sane, Timo

AU - De Menis, Ernesto

AU - Cannavò, Salvatore

AU - Gündogdu, Sadi

AU - Lucassen, Anneke

AU - Izatt, Louise

AU - Aylwin, Simon

AU - Bano, Gul

AU - Hodgson, Shirley

AU - Koch, Christian A

AU - Karhu, Auli

AU - Aaltonen, Lauri A

PY - 2008/10

Y1 - 2008/10

N2 - CONTEXT: Germline mutations in AIP have been recently shown to cause pituitary adenoma predisposition (PAP). Subsequently, many intragenic germline mutations have been reported, both in familial and in sporadic settings.OBJECTIVE: Our objective was to evaluate the possible contribution of large genomic germline AIP deletions, an important mutation type in tumor predisposition syndromes, in PAP.DESIGN: Here, we applied the multiplex ligation-dependent probe amplification assay to examine whether large genomic AIP or MEN1 alterations account for a subset of PAP cases.PATIENTS: The study was performed on familial and sporadic pituitary adenoma cases of European origin, which had previously tested negative for germline AIP and MEN1 mutations by sequencing.RESULTS: Two of 21 pituitary adenoma families (9.5%) were found to harbor an AIP deletion. No copy number changes were detected among 67 sporadic pituitary adenoma patients. No MEN1 deletions were found.CONCLUSIONS: The present study shows that large genomic AIP deletions account for a subset of PAP. Therefore, in suspected PAP cases undergoing counseling and AIP genetic testing, multiplex ligation-dependent probe amplification could be considered if direct sequencing does not identify a mutation.

AB - CONTEXT: Germline mutations in AIP have been recently shown to cause pituitary adenoma predisposition (PAP). Subsequently, many intragenic germline mutations have been reported, both in familial and in sporadic settings.OBJECTIVE: Our objective was to evaluate the possible contribution of large genomic germline AIP deletions, an important mutation type in tumor predisposition syndromes, in PAP.DESIGN: Here, we applied the multiplex ligation-dependent probe amplification assay to examine whether large genomic AIP or MEN1 alterations account for a subset of PAP cases.PATIENTS: The study was performed on familial and sporadic pituitary adenoma cases of European origin, which had previously tested negative for germline AIP and MEN1 mutations by sequencing.RESULTS: Two of 21 pituitary adenoma families (9.5%) were found to harbor an AIP deletion. No copy number changes were detected among 67 sporadic pituitary adenoma patients. No MEN1 deletions were found.CONCLUSIONS: The present study shows that large genomic AIP deletions account for a subset of PAP. Therefore, in suspected PAP cases undergoing counseling and AIP genetic testing, multiplex ligation-dependent probe amplification could be considered if direct sequencing does not identify a mutation.

KW - Adenoma/genetics

KW - Adolescent

KW - Adult

KW - Base Sequence

KW - DNA Mutational Analysis

KW - Family

KW - Female

KW - Gene Deletion

KW - Genetic Predisposition to Disease

KW - Germ-Line Mutation

KW - Humans

KW - Intracellular Signaling Peptides and Proteins/genetics

KW - Male

KW - Middle Aged

KW - Molecular Sequence Data

KW - Pituitary Neoplasms/genetics

KW - Precancerous Conditions/genetics

U2 - 10.1210/jc.2008-1003

DO - 10.1210/jc.2008-1003

M3 - Article

C2 - 18628514

SN - 0021-972X

VL - 93

SP - 4146

EP - 4151

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

IS - 10

ER -

Large genomic deletions in AIP in pituitary adenoma predisposition

Abstract

Keywords

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