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No evidence of RET germline mutations in familial pituitary adenoma

No evidence of RET germline mutations in familial pituitary adenoma
No evidence of RET germline mutations in familial pituitary adenoma

Pituitary adenomas are common in the general population. Although most of them are sporadic, some occur in a familial setting. In familial pituitary adenoma patients it is common that no germline defects are found after screening of aryl hydrocarbon receptor interacting protein (AIP) and other genes known to underlie the condition, suggesting the existence of yet unknown predisposition genes. Recently, the RET proto-oncogene was found to be a novel in vivo interaction partner of AIP in the pituitary gland. Here, we have screened patients from 16 AIP mutation negative (AIPmut-) pituitary adenoma families for RET germline mutations to assess whether RET could play a role in pituitary adenoma predisposition, similar to AIP. We found five novel germline RET changes: one in RET Exon 4 and the rest in noncoding regions of RET. Two changes, c.1560*G>A and -1285G>A, were segregated in affected family members. We also analyzed the RET region with enhancer element locator (EEL) to identify RET regulatory elements, and to see whether the changes resided in these. None of the variants mapped to the regions predicted by EEL. Expression of RET was examined in ten AIPmut- and seven AIP mutation positive (AIPmut+) somatotropinomas by immunohistochemistry, with a trend showing reduced expression in the latter (P=0.05). We conclude that the RET variants are presumably not related to pituitary adenoma predisposition, although reduced RET expression may play a role in AIP-related genesis of somatotropinomas.

0952-5041
1-8
Heliövaara, Elina
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Tuupanen, Sari
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Ahlsten, Manuel
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Hodgson, Shirley
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De Menis, Ernesto
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Kuismin, Outi
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Izatt, Louise
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Gardner, R. J.Mc Kinlay
ce4cdb4e-5b61-4416-bbce-15a177944d8c
Gundogdu, Sadi
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Lucassen, Anneke
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Arola, Johanna
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Tuomisto, Anne
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Mäkinen, Markus
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Karhu, Auli
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Aaltonen, Lauri A.
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Heliövaara, Elina
c5d4240e-9004-4463-9b71-89b5c52acded
Tuupanen, Sari
f2522a59-f70b-4d0f-94d5-ba1c69b4d587
Ahlsten, Manuel
a5cd7bfc-2f21-44ba-a732-b504410132de
Hodgson, Shirley
a9f6b2c4-f329-40b5-8b07-a74b3fdd1a0c
De Menis, Ernesto
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Kuismin, Outi
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Izatt, Louise
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Gardner, R. J.Mc Kinlay
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Gundogdu, Sadi
edf4d71b-8162-4483-9082-7aa14e4e8bac
Lucassen, Anneke
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Arola, Johanna
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Tuomisto, Anne
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Mäkinen, Markus
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Karhu, Auli
b0ebd43a-6a3b-477c-97e2-39bdca785073
Aaltonen, Lauri A.
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Heliövaara, Elina, Tuupanen, Sari, Ahlsten, Manuel, Hodgson, Shirley, De Menis, Ernesto, Kuismin, Outi, Izatt, Louise, Gardner, R. J.Mc Kinlay, Gundogdu, Sadi, Lucassen, Anneke, Arola, Johanna, Tuomisto, Anne, Mäkinen, Markus, Karhu, Auli and Aaltonen, Lauri A. (2011) No evidence of RET germline mutations in familial pituitary adenoma. Journal of Molecular Endocrinology, 46 (1), 1-8. (doi:10.1677/JME-10-0052).

Record type: Article

Abstract

Pituitary adenomas are common in the general population. Although most of them are sporadic, some occur in a familial setting. In familial pituitary adenoma patients it is common that no germline defects are found after screening of aryl hydrocarbon receptor interacting protein (AIP) and other genes known to underlie the condition, suggesting the existence of yet unknown predisposition genes. Recently, the RET proto-oncogene was found to be a novel in vivo interaction partner of AIP in the pituitary gland. Here, we have screened patients from 16 AIP mutation negative (AIPmut-) pituitary adenoma families for RET germline mutations to assess whether RET could play a role in pituitary adenoma predisposition, similar to AIP. We found five novel germline RET changes: one in RET Exon 4 and the rest in noncoding regions of RET. Two changes, c.1560*G>A and -1285G>A, were segregated in affected family members. We also analyzed the RET region with enhancer element locator (EEL) to identify RET regulatory elements, and to see whether the changes resided in these. None of the variants mapped to the regions predicted by EEL. Expression of RET was examined in ten AIPmut- and seven AIP mutation positive (AIPmut+) somatotropinomas by immunohistochemistry, with a trend showing reduced expression in the latter (P=0.05). We conclude that the RET variants are presumably not related to pituitary adenoma predisposition, although reduced RET expression may play a role in AIP-related genesis of somatotropinomas.

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Published date: 1 February 2011

Identifiers

Local EPrints ID: 469446
URI: http://eprints.soton.ac.uk/id/eprint/469446
ISSN: 0952-5041
PURE UUID: c399c49e-fc46-4801-bd98-ca0c7c3fdab6
ORCID for Anneke Lucassen: ORCID iD orcid.org/0000-0003-3324-4338

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Date deposited: 14 Sep 2022 16:52
Last modified: 17 Mar 2024 02:54

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Contributors

Author: Elina Heliövaara
Author: Sari Tuupanen
Author: Manuel Ahlsten
Author: Shirley Hodgson
Author: Ernesto De Menis
Author: Outi Kuismin
Author: Louise Izatt
Author: R. J.Mc Kinlay Gardner
Author: Sadi Gundogdu
Author: Anneke Lucassen ORCID iD
Author: Johanna Arola
Author: Anne Tuomisto
Author: Markus Mäkinen
Author: Auli Karhu
Author: Lauri A. Aaltonen

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