Frequency of TERT promoter mutations in human cancers

被引：698

作者：

Vinagre, Joao ^{[1
,2
]}

Almeida, Ana ^{[1
,2
]}

Populo, Helena ^{[1
]}

Batista, Rui ^{[1
]}

Lyra, Joana ^{[1
,3
]}

Pinto, Vasco ^{[1
,3
]}

Coelho, Ricardo ^{[1
,2
]}

Celestino, Ricardo ^{[1
]}

Prazeres, Hugo ^{[1
,4
]}

Lima, Luis ^{[2
,5
,6
,7
]}

Melo, Miguel ^{[8
,9
]}

da Rocha, Adriana Gaspar ^{[1
,3
]}

Preto, Ana ^{[1
,10
]}

Castro, Patricia ^{[1
]}

Castro, Ligia ^{[3
,11
]}

Pardal, Fernando ^{[12
]}

Lopes, Jose Manuel ^{[1
,3
,11
]}

Santos, Lucio Lara ^{[5
]}

Reis, Rui Manuel ^{[13
,14
]}

Cameselle-Teijeiro, Jose ^{[15
]}

Sobrinho-Simoes, Manuel ^{[1
,3
,11
]}

Lima, Jorge ^{[1
,3
]}

Maximo, Valdemar ^{[1
,3
]}

Soares, Paula ^{[1
,3
]}

机构：

[1] Univ Porto IPATIMUP, Inst Mol Pathol & Immunol, P-4200465 Oporto, Portugal

[2] Univ Porto, Inst Biomed Sci Abel Salazar, P-4050313 Oporto, Portugal

[3] Univ Porto, Fac Med, P-4200319 Oporto, Portugal

[4] EPE, IPOFG, Coimbra Ctr, Portuguese Inst Oncol, P-3000075 Coimbra, Portugal

[5] Portuguese Inst Oncol, Expt Pathol & Therapeut Grp, P-4200072 Oporto, Portugal

[6] Polytech Inst Porto, Hlth Sch, CISA, Nucleo Invest Farm, P-4400330 Vila Nova De Gaia, Portugal

[7] Portuguese League Canc Norte, Res Dept, P-4200177 Oporto, Portugal

[8] Univ Hosp Coimbra, Dept Endocrinol Diabet & Metab, P-3000075 Coimbra, Portugal

[9] Univ Coimbra, Fac Med, Unit Endocrinol, P-3000548 Coimbra, Portugal

[10] Univ Minho, Dept Biol, Ctr Mol & Environm Biol CBMA, P-4710057 Braga, Portugal

[11] Hosp Sao Joao, Dept Pathol, P-4200319 Oporto, Portugal

[12] Hosp Braga, Dept Pathol, P-4710243 Braga, Portugal

[13] Univ Minho, Sch Hlth Sci, Life & Hlth Sci Res Inst ICVS, P-4710057 Braga, Portugal

[14] Barretos Canc Hosp, Mol Oncol Res Ctr, BR-14784400 Sao Paulo, Brazil

[15] Univ Santiago de Compostela, IDIS, Fac Med, Clin Univ Hosp,Dept Pathol,SERGAS, Santiago De Compostela 15706, Spain

来源：

NATURE COMMUNICATIONS | 2013年 / 4卷

关键词：

TUMORS; TELOMERASE; DIAGNOSIS; PATHWAY; GNAQ;

D O I：

10.1038/ncomms3185

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Reactivation of telomerase has been implicated in human tumorigenesis, but the underlying mechanisms remain poorly understood. Here we report the presence of recurrent somatic mutations in the TERT promoter in cancers of the central nervous system (43%), bladder (59%), thyroid (follicular cell-derived, 10%) and skin (melanoma, 29%). In thyroid cancers, the presence of TERT promoter mutations (when occurring together with BRAF mutations) is significantly associated with higher TERT mRNA expression, and in glioblastoma we find a trend for increased telomerase expression in cases harbouring TERT promoter mutations. Both in thyroid cancers and glioblastoma, TERT promoter mutations are significantly associated with older age of the patients. Our results show that TERT promoter mutations are relatively frequent in specific types of human cancers, where they lead to enhanced expression of telomerase.

引用

页数：6

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