TERT promoter mutations occur frequently in gliomas and a subset of tumors derived from cells with low rates of self-renewal

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TERT promoter mutations occur frequently in gliomas and a subset of tumors derived from cells with low rates of self-renewal. / Killela, Patrick J.; Reitman, Zachary J.; Jiao, Yuchen; Bettegowda, Chetan; Agrawal, Nishant; Diaz Jr., Luis A.; Friedman, Allan H.; Friedman, Henry; Gallia, Gary L.; Giovanella, Beppino C.; Grollman, Arthur P.; He, Tong-Chuan; He, Yiping; Hruban, Ralph H.; Jallo, George I.; Mandahl, Nils; Meeker, Alan K.; Mertens, Fredrik; Netto, George J.; Rasheed, B. Ahmed; Riggins, Gregory J.; Rosenquist, Thomas A.; Schiffman, Mark; Shih, Ie-Ming; Theodorescu, Dan; Torbenson, Michael S.; Velculescu, Victor E.; Wang, Tian-Li; Wentzensen, Nicolas; Wood, Laura D.; Zhang, Ming; McLendon, Roger E.; Bigner, Darell D.; Kinzler, Kenneth W.; Vogelstein, Bert; Papadopoulos, Nickolas; Yan, Hai.

I: Proceedings of the National Academy of Sciences, Vol. 110, Nr. 15, 2013, s. 6021-6026.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Harvard

Killela, PJ, Reitman, ZJ, Jiao, Y, Bettegowda, C, Agrawal, N, Diaz Jr., LA, Friedman, AH, Friedman, H, Gallia, GL, Giovanella, BC, Grollman, AP, He, T-C, He, Y, Hruban, RH, Jallo, GI, Mandahl, N, Meeker, AK, Mertens, F, Netto, GJ, Rasheed, BA, Riggins, GJ, Rosenquist, TA, Schiffman, M, Shih, I-M, Theodorescu, D, Torbenson, MS, Velculescu, VE, Wang, T-L, Wentzensen, N, Wood, LD, Zhang, M, McLendon, RE, Bigner, DD, Kinzler, KW, Vogelstein, B, Papadopoulos, N & Yan, H 2013, 'TERT promoter mutations occur frequently in gliomas and a subset of tumors derived from cells with low rates of self-renewal', Proceedings of the National Academy of Sciences, vol. 110, nr. 15, s. 6021-6026. https://doi.org/10.1073/pnas.1303607110

APA

CBE

Killela PJ, Reitman ZJ, Jiao Y, Bettegowda C, Agrawal N, Diaz Jr. LA, Friedman AH, Friedman H, Gallia GL, Giovanella BC, Grollman AP, He T-C, He Y, Hruban RH, Jallo GI, Mandahl N, Meeker AK, Mertens F, Netto GJ, Rasheed BA, Riggins GJ, Rosenquist TA, Schiffman M, Shih I-M, Theodorescu D, Torbenson MS, Velculescu VE, Wang T-L, Wentzensen N, Wood LD, Zhang M, McLendon RE, Bigner DD, Kinzler KW, Vogelstein B, Papadopoulos N, Yan H. 2013. TERT promoter mutations occur frequently in gliomas and a subset of tumors derived from cells with low rates of self-renewal. Proceedings of the National Academy of Sciences. 110(15):6021-6026. https://doi.org/10.1073/pnas.1303607110

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Author

Killela, Patrick J. ; Reitman, Zachary J. ; Jiao, Yuchen ; Bettegowda, Chetan ; Agrawal, Nishant ; Diaz Jr., Luis A. ; Friedman, Allan H. ; Friedman, Henry ; Gallia, Gary L. ; Giovanella, Beppino C. ; Grollman, Arthur P. ; He, Tong-Chuan ; He, Yiping ; Hruban, Ralph H. ; Jallo, George I. ; Mandahl, Nils ; Meeker, Alan K. ; Mertens, Fredrik ; Netto, George J. ; Rasheed, B. Ahmed ; Riggins, Gregory J. ; Rosenquist, Thomas A. ; Schiffman, Mark ; Shih, Ie-Ming ; Theodorescu, Dan ; Torbenson, Michael S. ; Velculescu, Victor E. ; Wang, Tian-Li ; Wentzensen, Nicolas ; Wood, Laura D. ; Zhang, Ming ; McLendon, Roger E. ; Bigner, Darell D. ; Kinzler, Kenneth W. ; Vogelstein, Bert ; Papadopoulos, Nickolas ; Yan, Hai. / TERT promoter mutations occur frequently in gliomas and a subset of tumors derived from cells with low rates of self-renewal. I: Proceedings of the National Academy of Sciences. 2013 ; Vol. 110, Nr. 15. s. 6021-6026.

RIS

TY - JOUR

T1 - TERT promoter mutations occur frequently in gliomas and a subset of tumors derived from cells with low rates of self-renewal

AU - Killela, Patrick J.

AU - Reitman, Zachary J.

AU - Jiao, Yuchen

AU - Bettegowda, Chetan

AU - Agrawal, Nishant

AU - Diaz Jr., Luis A.

AU - Friedman, Allan H.

AU - Friedman, Henry

AU - Gallia, Gary L.

AU - Giovanella, Beppino C.

AU - Grollman, Arthur P.

AU - He, Tong-Chuan

AU - He, Yiping

AU - Hruban, Ralph H.

AU - Jallo, George I.

AU - Mandahl, Nils

AU - Meeker, Alan K.

AU - Mertens, Fredrik

AU - Netto, George J.

AU - Rasheed, B. Ahmed

AU - Riggins, Gregory J.

AU - Rosenquist, Thomas A.

AU - Schiffman, Mark

AU - Shih, Ie-Ming

AU - Theodorescu, Dan

AU - Torbenson, Michael S.

AU - Velculescu, Victor E.

AU - Wang, Tian-Li

AU - Wentzensen, Nicolas

AU - Wood, Laura D.

AU - Zhang, Ming

AU - McLendon, Roger E.

AU - Bigner, Darell D.

AU - Kinzler, Kenneth W.

AU - Vogelstein, Bert

AU - Papadopoulos, Nickolas

AU - Yan, Hai

PY - 2013

Y1 - 2013

N2 - Malignant cells, like all actively growing cells, must maintain their telomeres, but genetic mechanisms responsible for telomere maintenance in tumors have only recently been discovered. In particular, mutations of the telomere binding proteins alpha thalassemia/mental retardation syndrome X-linked (ATRX) or death-domain associated protein (DAXX) have been shown to underlie a telomere maintenance mechanism not involving telomerase (alternative lengthening of telomeres), and point mutations in the promoter of the telomerase reverse transcriptase (TERT) gene increase telomerase expression and have been shown to occur in melanomas and a small number of other tumors. To further define the tumor types in which this latter mechanism plays a role, we surveyed 1,230 tumors of 60 different types. We found that tumors could be divided into types with low (<15%) and high (>= 15%) frequencies of TERT promoter mutations. The nine TERT-high tumor types almost always originated in tissues with relatively low rates of self renewal, including melanomas, liposarcomas, hepatocellular carcinomas, urothelial carcinomas, squamous cell carcinomas of the tongue, medulloblastomas, and subtypes of gliomas (including 83% of primary glioblastoma, the most common brain tumor type). TERT and ATRX mutations were mutually exclusive, suggesting that these two genetic mechanisms confer equivalent selective growth advantages. In addition to their implications for understanding the relationship between telomeres and tumorigenesis, TERT mutations provide a biomarker that may be useful for the early detection of urinary tract and liver tumors and aid in the classification and prognostication of brain tumors.

AB - Malignant cells, like all actively growing cells, must maintain their telomeres, but genetic mechanisms responsible for telomere maintenance in tumors have only recently been discovered. In particular, mutations of the telomere binding proteins alpha thalassemia/mental retardation syndrome X-linked (ATRX) or death-domain associated protein (DAXX) have been shown to underlie a telomere maintenance mechanism not involving telomerase (alternative lengthening of telomeres), and point mutations in the promoter of the telomerase reverse transcriptase (TERT) gene increase telomerase expression and have been shown to occur in melanomas and a small number of other tumors. To further define the tumor types in which this latter mechanism plays a role, we surveyed 1,230 tumors of 60 different types. We found that tumors could be divided into types with low (<15%) and high (>= 15%) frequencies of TERT promoter mutations. The nine TERT-high tumor types almost always originated in tissues with relatively low rates of self renewal, including melanomas, liposarcomas, hepatocellular carcinomas, urothelial carcinomas, squamous cell carcinomas of the tongue, medulloblastomas, and subtypes of gliomas (including 83% of primary glioblastoma, the most common brain tumor type). TERT and ATRX mutations were mutually exclusive, suggesting that these two genetic mechanisms confer equivalent selective growth advantages. In addition to their implications for understanding the relationship between telomeres and tumorigenesis, TERT mutations provide a biomarker that may be useful for the early detection of urinary tract and liver tumors and aid in the classification and prognostication of brain tumors.

U2 - 10.1073/pnas.1303607110

DO - 10.1073/pnas.1303607110

M3 - Article

VL - 110

SP - 6021

EP - 6026

JO - Proceedings of the National Academy of Sciences

T2 - Proceedings of the National Academy of Sciences

JF - Proceedings of the National Academy of Sciences

SN - 1091-6490

IS - 15

ER -