TUTCRIS - Tampereen teknillinen yliopisto

TUTCRIS

Loss of SUFU function in familial multiple meningioma

Tutkimustuotosvertaisarvioitu

Standard

Loss of SUFU function in familial multiple meningioma. / Aavikko, Mervi; Li, Song Ping; Saarinen, Silva; Alhopuro, Pia; Kaasinen, Eevi; Morgunova, Ekaterina; Li, Yilong; Vesanen, Kari; Smith, Miriam J.; Evans, D. Gareth R; Pöyhönen, Minna; Kiuru, Anne; Auvinen, Anssi; Aaltonen, Lauri A.; Taipale, Jussi; Vahteristo, Pia.

julkaisussa: AMERICAN JOURNAL OF HUMAN GENETICS, Vuosikerta 91, Nro 3, 07.09.2012, s. 520-526.

Tutkimustuotosvertaisarvioitu

Harvard

Aavikko, M, Li, SP, Saarinen, S, Alhopuro, P, Kaasinen, E, Morgunova, E, Li, Y, Vesanen, K, Smith, MJ, Evans, DGR, Pöyhönen, M, Kiuru, A, Auvinen, A, Aaltonen, LA, Taipale, J & Vahteristo, P 2012, 'Loss of SUFU function in familial multiple meningioma', AMERICAN JOURNAL OF HUMAN GENETICS, Vuosikerta. 91, Nro 3, Sivut 520-526. https://doi.org/10.1016/j.ajhg.2012.07.015

APA

Aavikko, M., Li, S. P., Saarinen, S., Alhopuro, P., Kaasinen, E., Morgunova, E., ... Vahteristo, P. (2012). Loss of SUFU function in familial multiple meningioma. AMERICAN JOURNAL OF HUMAN GENETICS, 91(3), 520-526. https://doi.org/10.1016/j.ajhg.2012.07.015

Vancouver

Aavikko M, Li SP, Saarinen S, Alhopuro P, Kaasinen E, Morgunova E et al. Loss of SUFU function in familial multiple meningioma. AMERICAN JOURNAL OF HUMAN GENETICS. 2012 syys 7;91(3):520-526. https://doi.org/10.1016/j.ajhg.2012.07.015

Author

Aavikko, Mervi ; Li, Song Ping ; Saarinen, Silva ; Alhopuro, Pia ; Kaasinen, Eevi ; Morgunova, Ekaterina ; Li, Yilong ; Vesanen, Kari ; Smith, Miriam J. ; Evans, D. Gareth R ; Pöyhönen, Minna ; Kiuru, Anne ; Auvinen, Anssi ; Aaltonen, Lauri A. ; Taipale, Jussi ; Vahteristo, Pia. / Loss of SUFU function in familial multiple meningioma. Julkaisussa: AMERICAN JOURNAL OF HUMAN GENETICS. 2012 ; Vuosikerta 91, Nro 3. Sivut 520-526.

Bibtex - Lataa

@article{7e222a5e360a4ff4a3ea519e5ffb3120,
title = "Loss of SUFU function in familial multiple meningioma",
abstract = "Meningiomas are the most common primary tumors of the CNS and account for up to 30{\%} of all CNS tumors. An increased risk of meningiomas has been associated with certain tumor-susceptibility syndromes, especially neurofibromatosis type II, but no gene defects predisposing to isolated familial meningiomas have thus far been identified. Here, we report on a family of five meningioma-affected siblings, four of whom have multiple tumors. No NF2 mutations were identified in the germline or tumors. We combined genome-wide linkage analysis and exome sequencing, and we identified in suppressor of fused homolog (Drosophila), SUFU, a c.367C>T (p.Arg123Cys) mutation segregating with the meningiomas in the family. The variation was not present in healthy controls, and all seven meningiomas analyzed displayed loss of the wild-type allele according to the classic two-hit model for tumor-suppressor genes. In silico modeling predicted the variant to affect the tertiary structure of the protein, and functional analyses showed that the activity of the altered SUFU was significantly reduced and therefore led to dysregulated hedgehog (Hh) signaling. SUFU is a known tumor-suppressor gene previously associated with childhood medulloblastoma predisposition. Our genetic and functional analyses indicate that germline mutations in SUFU also predispose to meningiomas, particularly to multiple meningiomas. It is possible that other genic mutations resulting in aberrant activation of the Hh pathway might underlie meningioma predisposition in families with an unknown etiology.",
author = "Mervi Aavikko and Li, {Song Ping} and Silva Saarinen and Pia Alhopuro and Eevi Kaasinen and Ekaterina Morgunova and Yilong Li and Kari Vesanen and Smith, {Miriam J.} and Evans, {D. Gareth R} and Minna P{\"o}yh{\"o}nen and Anne Kiuru and Anssi Auvinen and Aaltonen, {Lauri A.} and Jussi Taipale and Pia Vahteristo",
year = "2012",
month = "9",
day = "7",
doi = "10.1016/j.ajhg.2012.07.015",
language = "English",
volume = "91",
pages = "520--526",
journal = "AMERICAN JOURNAL OF HUMAN GENETICS",
issn = "0002-9297",
publisher = "Elsevier",
number = "3",

}

RIS (suitable for import to EndNote) - Lataa

TY - JOUR

T1 - Loss of SUFU function in familial multiple meningioma

AU - Aavikko, Mervi

AU - Li, Song Ping

AU - Saarinen, Silva

AU - Alhopuro, Pia

AU - Kaasinen, Eevi

AU - Morgunova, Ekaterina

AU - Li, Yilong

AU - Vesanen, Kari

AU - Smith, Miriam J.

AU - Evans, D. Gareth R

AU - Pöyhönen, Minna

AU - Kiuru, Anne

AU - Auvinen, Anssi

AU - Aaltonen, Lauri A.

AU - Taipale, Jussi

AU - Vahteristo, Pia

PY - 2012/9/7

Y1 - 2012/9/7

N2 - Meningiomas are the most common primary tumors of the CNS and account for up to 30% of all CNS tumors. An increased risk of meningiomas has been associated with certain tumor-susceptibility syndromes, especially neurofibromatosis type II, but no gene defects predisposing to isolated familial meningiomas have thus far been identified. Here, we report on a family of five meningioma-affected siblings, four of whom have multiple tumors. No NF2 mutations were identified in the germline or tumors. We combined genome-wide linkage analysis and exome sequencing, and we identified in suppressor of fused homolog (Drosophila), SUFU, a c.367C>T (p.Arg123Cys) mutation segregating with the meningiomas in the family. The variation was not present in healthy controls, and all seven meningiomas analyzed displayed loss of the wild-type allele according to the classic two-hit model for tumor-suppressor genes. In silico modeling predicted the variant to affect the tertiary structure of the protein, and functional analyses showed that the activity of the altered SUFU was significantly reduced and therefore led to dysregulated hedgehog (Hh) signaling. SUFU is a known tumor-suppressor gene previously associated with childhood medulloblastoma predisposition. Our genetic and functional analyses indicate that germline mutations in SUFU also predispose to meningiomas, particularly to multiple meningiomas. It is possible that other genic mutations resulting in aberrant activation of the Hh pathway might underlie meningioma predisposition in families with an unknown etiology.

AB - Meningiomas are the most common primary tumors of the CNS and account for up to 30% of all CNS tumors. An increased risk of meningiomas has been associated with certain tumor-susceptibility syndromes, especially neurofibromatosis type II, but no gene defects predisposing to isolated familial meningiomas have thus far been identified. Here, we report on a family of five meningioma-affected siblings, four of whom have multiple tumors. No NF2 mutations were identified in the germline or tumors. We combined genome-wide linkage analysis and exome sequencing, and we identified in suppressor of fused homolog (Drosophila), SUFU, a c.367C>T (p.Arg123Cys) mutation segregating with the meningiomas in the family. The variation was not present in healthy controls, and all seven meningiomas analyzed displayed loss of the wild-type allele according to the classic two-hit model for tumor-suppressor genes. In silico modeling predicted the variant to affect the tertiary structure of the protein, and functional analyses showed that the activity of the altered SUFU was significantly reduced and therefore led to dysregulated hedgehog (Hh) signaling. SUFU is a known tumor-suppressor gene previously associated with childhood medulloblastoma predisposition. Our genetic and functional analyses indicate that germline mutations in SUFU also predispose to meningiomas, particularly to multiple meningiomas. It is possible that other genic mutations resulting in aberrant activation of the Hh pathway might underlie meningioma predisposition in families with an unknown etiology.

UR - http://www.scopus.com/inward/record.url?scp=84866100107&partnerID=8YFLogxK

U2 - 10.1016/j.ajhg.2012.07.015

DO - 10.1016/j.ajhg.2012.07.015

M3 - Article

VL - 91

SP - 520

EP - 526

JO - AMERICAN JOURNAL OF HUMAN GENETICS

JF - AMERICAN JOURNAL OF HUMAN GENETICS

SN - 0002-9297

IS - 3

ER -