SOX2 haploinsufficiency is associated with slow progressing hypothalamo-pituitary tumours

被引：34

作者：

Alatzoglou, Kyriaki S. ^{[1
]}

Andoniadou, Cynthia L. ^{[2
]}

Kelberman, Daniel ^{[3
]}

Buchanan, Charles R. ^{[4
]}

Crolla, John ^{[5
]}

Cristina Arriazu, Maria ^{[6
]}

Roubicek, Martin ^{[6
]}

Moncet, Daniel ^{[6
]}

Martinez-Barbera, Juan P. ^{[2
]}

Dattani, Mehul T. ^{[1
]}

机构：

[1] UCL, Dev Endocrinol Res Grp, Clin & Mol Genet Unit, Inst Child Hlth, London WC1N 1EH, England

[2] UCL, Neural Dev Unit, Inst Child Hlth, London WC1N 1EH, England

[3] UCL, Ulverscroft Vis Res Grp, Dev Biol Unit, Inst Child Hlth, London WC1N 1EH, England

[4] Kings Coll Hosp NHS Fdn Trust, Dept Child Hlth, London, England

[5] Salisbury Dist Hosp, Wessex Reg Genet Lab, Salisbury, Wilts, England

[6] Hosp Privado Comunidad Mar Del Plata, Dept Pediat Endocrinol, Buenos Aires, DF, Argentina

来源：

HUMAN MUTATION | 2011年 / 32卷 / 12期

基金：

英国惠康基金;

关键词：

SOX2; pituitary; tumors; ss-catenin; TRANSCRIPTION FACTOR SOX2; BETA-CATENIN; WNT PATHWAY; EXPRESSION; PITUITARY; MUTATIONS; SURVIVAL; COMPLEX; LUNG; SRY;

D O I：

10.1002/humu.21606

中图分类号：

Q3 [遗传学];

学科分类号：

071007 [遗传学];

摘要：

SOX2 is an early developmental transcription factor and marker of stem cells that has recently been implicated in the development of the pituitary gland. Heterozygous SOX2 mutations have been described in patients with hypopituitarism and severe ocular abnormalities. In the majority of published cases, the pituitary gland is either small or normal in size. Here, we report two unrelated patients with SOX2 haploinsufficiency (a heterozygous gene deletion and a novel c.143TC > AA/p.F48X mutation) who developed nonprogressive pituitary tumors of early onset, suggesting a congenital etiology. The truncating mutation resulted in significant loss of function and impaired nuclear localization of the mutant protein, in addition to a failure to repress beta-catenin transcriptional activity in vitro. This is the first indication that SOX2 haploinsufficiency is implicated in the generation of pituitary tumors with distinct clinical characteristics, possibly mediated via its effects on the Wnt signaling pathway. 32:13761380, 2011. (C) 2011 Wiley Periodicals, Inc.

引用

页码：1376 / 1380

页数：5

共 29 条

[1]

SOX2 is an amplified lineage-survival oncogene in lung and esophageal squamous cell carcinomas [J].

Bass, Adam J. ;

Watanabe, Hideo ;

Mermel, Craig H. ;

Yu, Soyoung ;

Perner, Sven ;

Verhaak, Roel G. ;

Kim, So Young ;

Wardwell, Leslie ;

Tamayo, Pablo ;

Gat-Viks, Irit ;

Ramos, Alex H. ;

Woo, Michele S. ;

Weir, Barbara A. ;

Getz, Gad ;

Beroukhim, Rameen ;

O'Kelly, Michael ;

Dutt, Amit ;

Rozenblatt-Rosen, Orit ;

Dziunycz, Piotr ;

Komisarof, Justin ;

Chirieac, Lucian R. ;

LaFargue, Christopher J. ;

Scheble, Veit ;

Wilbertz, Theresia ;

Ma, Changqing ;

Rao, Shilpa ;

Nakagawa, Hiroshi ;

Stairs, Douglas B. ;

Lin, Lin ;

Giordano, Thomas J. ;

Wagner, Patrick ;

Minna, John D. ;

Gazdar, Adi F. ;

Zhu, Chang Qi ;

Brose, Marcia S. ;

Cecconello, Ivan ;

Ribeiro, Ulysses, Jr. ;

Marie, Suely K. ;

Dahl, Olav ;

Shivdasani, Ramesh A. ;

Tsao, Ming-Sound ;

Rubin, Mark A. ;

Wong, Kwok K. ;

Regev, Aviv ;

Hahn, William C. ;

Beer, David G. ;

Rustgi, Anil K. ;

Meyerson, Matthew .

NATURE GENETICS, 2009, 41 (11) :1238-U105

[2]

Common mutations of β-catenin in adamantinomatous craniopharyngiomas but not in other tumours originating from the sellar region [J].

Buslei, R ;

Nolde, M ;

Hofmann, B ;

Meissner, S ;

Eyupoglu, IY ;

Siebzehnrübl, F ;

Hahnen, E ;

Kreutzer, J ;

Fahlbusch, R .

ACTA NEUROPATHOLOGICA, 2005, 109 (06) :589-597

[3]

The molecular mechanism governing the oncogenic potential of SOX2 in breast cancer [J].

Chen, Yupeng ;

Shi, Lei ;

Zhang, Lirong ;

Li, Ruifang ;

Liang, Jing ;

Yu, Wenhua ;

Sun, Luyang ;

Yang, Xiaohan ;

Wang, Yan ;

Zhang, Yu ;

Shang, Yongfeng .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2008, 283 (26) :17969-17978

[4]

Collignon J, 1996, DEVELOPMENT, V122, P509

[5]

Complex humoral immune response against a benign tumor: Frequent antibody response against specific antigens as diagnostic targets [J].

Comtesse, N ;

Zippel, A ;

Walle, S ;

Monz, D ;

Backes, C ;

Fischer, U ;

Mayer, J ;

Ludwig, N ;

Hildebrandt, A ;

Keller, A ;

Steudel, WI ;

Lenhof, HP ;

Meese, E .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (27) :9601-9606

[6]

Wnt pathway inhibitors are strongly down-regulated in pituitary tumors [J].

Elston, Marianne S. ;

Gill, Anthony J. ;

Conaglen, John V. ;

Clarkson, Adele ;

Shaw, Janet M. ;

Law, Andrew J. J. ;

Cook, Raymond J. ;

Little, Nicholas S. ;

Clifton-Bligh, Roderick J. ;

Robinson, Bruce G. ;

McDonald, Kerrie L. .

ENDOCRINOLOGY, 2008, 149 (03) :1235-1242

[7]

Characterization of cis-regulatory elements of the homeobox gene Xanf-1 [J].

Eroshkin, F ;

Kazanskaya, O ;

Martynova, N ;

Zaraisky, A .

GENE, 2002, 285 (1-2) :279-286

[8]

SOX2-expressing progenitor cells generate all of the major cell types in the adult mouse pituitary gland [J].

Fauquier, Teddy ;

Rizzoti, Karine ;

Dattani, Mehul ;

Lovell-Badge, Robin ;

Robinson, Iain C. A. F. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (08) :2907-2912

[9]

Recurrent Copy Number Gain of Transcription Factor SOX2 and Corresponding High Protein Expression in Oral Squamous Cell Carcinoma [J].

Freier, Koija ;

Knoepfle, Karl ;

Flechtenmacher, Christa ;

Pungs, Susanne ;

Devens, Frauke ;

Toedt, Grischa ;

Hofele, Christof ;

Joos, Stefan ;

Lichter, Peter ;

Radwirnmer, Bernhard .

GENES CHROMOSOMES & CANCER, 2010, 49 (01) :9-16

[10]

Increased Wingless (Wnt) signaling in pituitary progenitor/stem cells gives rise to pituitary tumors in mice and humans [J].

Gaston-Massuet, Carles ;

Andoniadou, Cynthia Lilian ;

Signore, Massimo ;

Jayakody, Sujatha A. ;

Charolidi, Nicoletta ;

Kyeyune, Roger ;

Vernay, Bertrand ;

Jacques, Thomas S. ;

Taketo, Makoto Mark ;

Le Tissier, Paul ;

Dattani, Mehul T. ;

Martinez-Barbera, Juan Pedro .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2011, 108 (28) :11482-11487

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