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117 results on '"Boisselier B"'

7. Clinical value of chromosome arms 19q and 11p losses in low-grade gliomas

Author

Alentorn, A., Thuijl, H.F. van, Marie, Y., Alshehhi, H., Carpentier, C., Boisselier, B., Laigle-Donadey, F., Mokhtari, K., Scheinin, I., Wesseling, P., Ylstra, B., Capelle, L., Hoang-Xuan, K., Sanson, M., Delattre, J.Y., Reijneveld, J.C., Idbaih, A., Alentorn, A., Thuijl, H.F. van, Marie, Y., Alshehhi, H., Carpentier, C., Boisselier, B., Laigle-Donadey, F., Mokhtari, K., Scheinin, I., Wesseling, P., Ylstra, B., Capelle, L., Hoang-Xuan, K., Sanson, M., Delattre, J.Y., Reijneveld, J.C., and Idbaih, A.

Abstract

Item does not contain fulltext, BACKGROUND: Diffuse low-grade gliomas (LGGs) form a heterogeneous subgroup of gliomas in adults. Chromosome (chr) arms 1p/19q codeletion and IDH mutation have been shown to be closely associated with oligodendroglial phenotype and better prognosis. We sought to identify relevant biomarkers in non 1p/19q codeleted LGGs. METHODS: We characterized a retrospective series of 126 LGGs using genomic arrays, microsatellite analysis, IDH sequencing, MGMT promoter methylation assay, and p53 expression analysis. RESULTS: Our study confirms that 1p/19q codeletion, mutually exclusive with p53 overexpression, was associated with: (i) better prognosis, (ii) oligodendroglial phenotype, (iii) MGMT promoter methylation, and (iv) IDH mutation. Interestingly, 1p/19q codeleted tumors occur in older patients at diagnosis. Our study shows that non 1p/19q codeleted LGGs can be divided in 5 main genomic subgroups: (i) 11p loss, (ii) 19q loss (iii) 7 gain, (iv) 19 gain, and (v) unclassified. In non 1p/19q codeleted LGGs, we demonstrated that (i) 11p loss is associated with astrocytoma phenotype and has an independent negative prognostic value, and (ii) 19q loss diminished the favorable prognostic value of IDH mutation. Our findings were validated in an independent cohort of 98 LGGs. CONCLUSION: Novel genomic entities and biomarkers have been identified in non 1p/19q codeleted LGGs. Our findings may help to stratify non 1p/19q codeleted LGGs, facilitating future individualization of treatment. Further prospective studies are warranted to support our findings.

Published
2014

8. Genome-wide association study identifies five susceptibility loci for glioma

Author

Shete, S, Hosking, F J, Robertson, L B, Dobbins, S E, Sanson, M, Malmer, B, Simon, M, Marie, Y, Boisselier, B, Delattre, J Y, Hoang-Xuan, K, El Hallani, S, Idbaih, A, Zelenika, D, Andersson, U, Henriksson, R, Bergenheim, A T, Feychting, M, Lönn, S, Ahlbom, A, Schramm, J, Linnebank, M, Hemminki, K, Kumar, R, Hepworth, S J, Price, A, Armstrong, G, Liu, Y, Gu, X, Yu, R, Lau, C, Schoemaker, M, Muir, K, Swerdlow, A, Lathrop, M, Bondy, M, Houlston, R S, and University of Zurich

Subjects
1311 Genetics, 610 Medicine & health, 10040 Clinic for Neurology
Published
2009

9. TERT promoter mutations in gliomas, genetic associations and clinico-pathological correlations

Author

Labussière, M, primary, Di Stefano, A L, additional, Gleize, V, additional, Boisselier, B, additional, Giry, M, additional, Mangesius, S, additional, Bruno, A, additional, Paterra, R, additional, Marie, Y, additional, Rahimian, A, additional, Finocchiaro, G, additional, Houlston, R S, additional, Hoang-Xuan, K, additional, Idbaih, A, additional, Delattre, J-Y, additional, Mokhtari, K, additional, and Sanson, M, additional

Published
2014
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13. PATHOLOGY

Author

Adachi, J.-i., primary, Totake, K., additional, Shirahata, M., additional, Mishima, K., additional, Suzuki, T., additional, Yanagisawa, T., additional, Fukuoka, K., additional, Nishikawa, R., additional, Arimappamagan, A., additional, Manoj, N., additional, Mahadevan, A., additional, Bhat, D., additional, Arvinda, H., additional, Indiradevi, B., additional, Somanna, S., additional, Chandramouli, B., additional, Petterson, S. A., additional, Hermansen, S. K., additional, Dahlrot, R. H., additional, Hansen, S., additional, Kristensen, B. W., additional, Carvalho, F., additional, Jalali, S., additional, Singh, S., additional, Croul, S., additional, Aldape, K., additional, Zadeh, G., additional, Choi, J., additional, Park, S.-H., additional, Khang, S. K., additional, Suh, Y.-L., additional, Kim, S. P., additional, Lee, Y. S., additional, Kim, S. H., additional, Coberly, S., additional, Samayoa, K., additional, Liu, Y., additional, Kiaei, P., additional, Hill, J., additional, Patterson, S., additional, Damore, M., additional, Dahiya, S., additional, Emnett, R., additional, Phillips, J., additional, Haydon, D., additional, Leonard, J., additional, Perry, A., additional, Gutmann, D., additional, Epari, S., additional, Ahmed, S., additional, Gurav, M., additional, Raikar, S., additional, Moiyadi, A., additional, Shetty, P., additional, Gupta, T., additional, Jalali, R., additional, Georges, J., additional, Zehri, A., additional, Carlson, E., additional, Martirosyan, N., additional, Elhadi, A., additional, Nichols, J., additional, Ighaffari, L., additional, Eschbacher, J., additional, Feuerstein, B., additional, Anderson, T., additional, Preul, M., additional, Jensen, K., additional, Nakaji, P., additional, Girardi, H., additional, Monville, F., additional, Carpentier, S., additional, Giry, M., additional, Voss, J., additional, Jenkins, R., additional, Boisselier, B., additional, Frayssinet, V., additional, Poggionovo, C., additional, Catteau, A., additional, Mokhtari, K., additional, Sanson, M., additional, Peyro-Saint-Paul, H., additional, Giannini, C., additional, Hide, T., additional, Nakamura, H., additional, Makino, K., additional, Yano, S., additional, Anai, S., additional, Shinojima, N., additional, Kuroda, J.-i., additional, Takezaki, T., additional, Kuratsu, J.-i., additional, Higuchi, F., additional, Matsuda, H., additional, Iwata, K., additional, Ueki, K., additional, Kim, P., additional, Kong, J., additional, Cooper, L., additional, Wang, F., additional, Gao, J., additional, Teodoro, G., additional, Scarpace, L., additional, Mikkelsen, T., additional, Schniederjan, M., additional, Moreno, C., additional, Saltz, J., additional, Brat, D., additional, Cho, U., additional, Hong, Y.-K., additional, Lober, R., additional, Lu, L., additional, Gephart, M. H., additional, Fisher, P., additional, Miyazaki, M., additional, Nishihara, H., additional, Itoh, T., additional, Kato, M., additional, Fujimoto, S., additional, Kimura, T., additional, Tanino, M., additional, Tanaka, S., additional, Nguyen, N., additional, Moes, G., additional, Villano, J. L., additional, Kanno, H., additional, Kato, Y., additional, Ohnishi, T., additional, Harada, H., additional, Ohue, S., additional, Kouno, S., additional, Inoue, A., additional, Yamashita, D., additional, Okamoto, S., additional, Nitta, M., additional, Muragaki, Y., additional, Maruyama, T., additional, Sawada, T., additional, Komori, T., additional, Saito, T., additional, Okada, Y., additional, Omay, S. B., additional, Gunel, J. M., additional, Clark, V. E., additional, Li, J., additional, Omay, E. Z. E., additional, Serin, A., additional, Kolb, L. E., additional, Hebert, R. M., additional, Bilguvar, K., additional, Ozduman, K., additional, Pamir, M. N., additional, Kilic, T., additional, Baehring, J., additional, Piepmeier, J. M., additional, Brennan, C. W., additional, Huse, J., additional, Gutin, P. H., additional, Yasuno, K., additional, Vortmeyer, A., additional, Gunel, M., additional, Pugh, S., additional, Rogers, C. L., additional, Brachman, D., additional, McMillan, W., additional, Jenrette, J., additional, Barani, I., additional, Shrieve, D., additional, Sloan, A., additional, Mehta, M., additional, Prabowo, A., additional, Iyer, A., additional, Veersema, T., additional, Anink, J., additional, Meeteren, A. S.-v., additional, Spliet, W., additional, van Rijen, P., additional, Ferrier, T., additional, Capper, D., additional, Thom, M., additional, Aronica, E., additional, Chharchhodawala, T., additional, Sable, M., additional, Sharma, M. C., additional, Sarkar, C., additional, Suri, V., additional, Singh, M., additional, Santosh, V., additional, Thota, B., additional, Srividya, M., additional, Sravani, K., additional, Shwetha, S., additional, Arivazhagan, A., additional, Thennarasu, K., additional, Hegde, A., additional, Kondaiah, P., additional, Somasundaram, K., additional, Rao, M., additional, Kumar, V. P., additional, Shastry, A., additional, Narayan, R., additional, Naz, S., additional, Venneti, S., additional, Garimella, M., additional, Sullivan, L., additional, Martinez, D., additional, Heguy, A., additional, Santi, M., additional, Thompson, C., additional, Judkins, A., additional, Voronovich, Z., additional, Chen, L., additional, Clark, K., additional, Walsh, M., additional, Mannas, J., additional, Horbinski, C., additional, Wiestler, B., additional, Holland-Letz, T., additional, Korshunov, A., additional, von Deimling, A., additional, Pfister, S. M., additional, Platten, M., additional, Weller, M., additional, Wick, W., additional, Zieman, G., additional, Dardis, C., additional, and Ashby, L., additional

Published
2013
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14. OMICS AND PROGNSTIC MARKERS

Author

Adachi, K., primary, Sasaki, H., additional, Nagahisa, S., additional, Yoshida, K., additional, Hattori, N., additional, Nishiyama, Y., additional, Kawase, T., additional, Hasegawa, M., additional, Abe, M., additional, Hirose, Y., additional, Alentorn, A., additional, Marie, Y., additional, Poggioli, S., additional, Alshehhi, H., additional, Boisselier, B., additional, Carpentier, C., additional, Mokhtari, K., additional, Capelle, L., additional, Figarella-Branger, D., additional, Hoang-Xuan, K., additional, Sanson, M., additional, Delattre, J.-Y., additional, Idbaih, A., additional, Yust-Katz, S., additional, Anderson, M., additional, Olar, A., additional, Eterovic, A., additional, Ezzeddine, N., additional, Chen, K., additional, Zhao, H., additional, Fuller, G., additional, Aldape, K., additional, de Groot, J., additional, Andor, N., additional, Harness, J., additional, Lopez, S. G., additional, Fung, T. L., additional, Mewes, H. W., additional, Petritsch, C., additional, Arivazhagan, A., additional, Somasundaram, K., additional, Thennarasu, K., additional, Pandey, P., additional, Anandh, B., additional, Santosh, V., additional, Chandramouli, B., additional, Hegde, A., additional, Kondaiah, P., additional, Rao, M., additional, Bell, R., additional, Kang, R., additional, Hong, C., additional, Song, J., additional, Costello, J., additional, Nagarajan, R., additional, Zhang, B., additional, Diaz, A., additional, Wang, T., additional, Bie, L., additional, Li, Y., additional, Liu, H., additional, Luyo, W. F. C., additional, Carnero, M. H., additional, Iruegas, M. E. P., additional, Morell, A. R., additional, Figueiras, M. C., additional, Lopez, R. L., additional, Valverde, C. F., additional, Chan, A. K.-Y., additional, Pang, J. C.-S., additional, Chung, N. Y.-F., additional, Li, K. K.-W., additional, Poon, W. S., additional, Chan, D. T.-M., additional, Wang, Y., additional, Ng, H.-a. K., additional, Chaumeil, M., additional, Larson, P., additional, Yoshihara, H., additional, Vigneron, D., additional, Nelson, S., additional, Pieper, R., additional, Phillips, J., additional, Ronen, S., additional, Clark, V., additional, Omay, Z. E., additional, Serin, A., additional, Gunel, J., additional, Omay, B., additional, Grady, C., additional, Youngblood, M., additional, Bilguvar, K., additional, Baehring, J., additional, Piepmeier, J., additional, Gutin, P., additional, Vortmeyer, A., additional, Brennan, C., additional, Pamir, M. N., additional, Kilic, T., additional, Krischek, B., additional, Simon, M., additional, Yasuno, K., additional, Gunel, M., additional, Cohen, A. L., additional, Sato, M., additional, Aldape, K. D., additional, Mason, C., additional, Diefes, K., additional, Heathcock, L., additional, Abegglen, L., additional, Shrieve, D., additional, Couldwell, W., additional, Schiffman, J. D., additional, Colman, H., additional, D'Alessandris, Q. G., additional, Cenci, T., additional, Martini, M., additional, Ricci-Vitiani, L., additional, De Maria, R., additional, Larocca, L. M., additional, Pallini, R., additional, Theeler, B., additional, Lang, F., additional, Rao, G., additional, Gilbert, M., additional, Sulman, E., additional, Luthra, R., additional, Eterovic, K., additional, Routbort, M., additional, Verhaak, R., additional, Mills, G., additional, Mendelsohn, J., additional, Meric-Bernstam, F., additional, Yung, A., additional, MacArthur, K., additional, Hahn, S., additional, Kao, G., additional, Lustig, R., additional, Alonso-Basanta, M., additional, Chandrasekaran, S., additional, Wileyto, E. P., additional, Reyes, E., additional, Dorsey, J., additional, Fujii, K., additional, Kurozumi, K., additional, Ichikawa, T., additional, Onishi, M., additional, Ishida, J., additional, Shimazu, Y., additional, Kaur, B., additional, Chiocca, E. A., additional, Date, I., additional, Geisenberger, C., additional, Mock, A., additional, Warta, R., additional, Schwager, C., additional, Hartmann, C., additional, von Deimling, A., additional, Abdollahi, A., additional, Herold-Mende, C., additional, Gevaert, O., additional, Achrol, A., additional, Gholamin, S., additional, Mitra, S., additional, Westbroek, E., additional, Loya, J., additional, Mitchell, L., additional, Chang, S., additional, Steinberg, G., additional, Plevritis, S., additional, Cheshier, S., additional, Xu, J., additional, Napel, S., additional, Zaharchuk, G., additional, Harsh, G., additional, Gutman, D., additional, Holder, C., additional, Colen, R., additional, Dunn, W., additional, Jain, R., additional, Cooper, L., additional, Hwang, S., additional, Flanders, A., additional, Brat, D., additional, Hayes, J., additional, Droop, A., additional, Thygesen, H., additional, Boissinot, M., additional, Westhead, D., additional, Short, S., additional, Lawler, S., additional, Bady, P., additional, Kurscheid, S., additional, Delorenzi, M., additional, Hegi, M. E., additional, Crosby, C., additional, Faulkner, C., additional, Smye-Rumsby, T., additional, Kurian, K., additional, Williams, M., additional, Hopkins, K., additional, Palmer, A., additional, Williams, H., additional, Wragg, C., additional, Haynes, H. R., additional, Kurian, K. M., additional, White, P., additional, Oka, T., additional, Jalbert, L., additional, Elkhaled, A., additional, Jensen, R., additional, Salzman, K., additional, Schabel, M., additional, Gillespie, D., additional, Mumert, M., additional, Johnson, B., additional, Mazor, T., additional, Barnes, M., additional, Yamamoto, S., additional, Ueda, H., additional, Tatsuno, K., additional, Aihara, K., additional, Bollen, A., additional, Hirst, M., additional, Marra, M., additional, Mukasa, A., additional, Saito, N., additional, Aburatani, H., additional, Berger, M., additional, Taylor, B., additional, Popov, S., additional, Mackay, A., additional, Ingram, W., additional, Burford, A., additional, Jury, A., additional, Vinci, M., additional, Jones, C., additional, Jones, D. T. W., additional, Hovestadt, V., additional, Picelli, S., additional, Wang, W., additional, Northcott, P. A., additional, Kool, M., additional, Reifenberger, G., additional, Pietsch, T., additional, Sultan, M., additional, Lehrach, H., additional, Yaspo, M.-L., additional, Borkhardt, A., additional, Landgraf, P., additional, Eils, R., additional, Korshunov, A., additional, Zapatka, M., additional, Radlwimmer, B., additional, Pfister, S. M., additional, Lichter, P., additional, Joy, A., additional, Smirnov, I., additional, Reiser, M., additional, Shapiro, W., additional, Kim, S., additional, Feuerstein, B., additional, Jungk, C., additional, Friauf, S., additional, Unterberg, A., additional, Juratli, T. A., additional, McElroy, J., additional, Meng, W., additional, Huebner, A., additional, Geiger, K. D., additional, Krex, D., additional, Schackert, G., additional, Chakravarti, A., additional, Lautenschlaeger, T., additional, Kim, B. Y., additional, Jiang, W., additional, Beiko, J., additional, Prabhu, S., additional, DeMonte, F., additional, Sawaya, R., additional, Cahill, D., additional, McCutcheon, I., additional, Lau, C., additional, Wang, L., additional, Terashima, K., additional, Yamaguchi, S., additional, Burstein, M., additional, Sun, J., additional, Suzuki, T., additional, Nishikawa, R., additional, Nakamura, H., additional, Natsume, A., additional, Terasaka, S., additional, Ng, H.-K., additional, Muzny, D., additional, Gibbs, R., additional, Wheeler, D., additional, Zhang, X.-q., additional, Sun, S., additional, Lam, K.-f., additional, Kiang, K. M. Y., additional, Pu, J. K. S., additional, Ho, A. S. W., additional, Leung, G. K. K., additional, Loebel, F., additional, Curry, W. T., additional, Barker, F. G., additional, Lelic, N., additional, Chi, A. S., additional, Cahill, D. P., additional, Lu, D., additional, Yin, J., additional, Teo, C., additional, McDonald, K., additional, Madhankumar, A., additional, Weston, C., additional, Slagle-Webb, B., additional, Sheehan, J., additional, Patel, A., additional, Glantz, M., additional, Connor, J., additional, Maire, C., additional, Francis, J., additional, Zhang, C.-Z., additional, Jung, J., additional, Manzo, V., additional, Adalsteinsson, V., additional, Homer, H., additional, Blumenstiel, B., additional, Pedamallu, C. S., additional, Nickerson, E., additional, Ligon, A., additional, Love, C., additional, Meyerson, M., additional, Ligon, K., additional, Jalbert, L. E., additional, Nelson, S. J., additional, Bollen, A. W., additional, Smirnov, I. V., additional, Song, J. S., additional, Olshen, A. B., additional, Berger, M. S., additional, Chang, S. M., additional, Taylor, B. S., additional, Costello, J. F., additional, Mehta, S., additional, Armstrong, B., additional, Peng, S., additional, Bapat, A., additional, Berens, M., additional, Melendez, B., additional, Mollejo, M., additional, Mur, P., additional, Hernandez-Iglesias, T., additional, Fiano, C., additional, Ruiz, J., additional, Rey, J. A., additional, Stadler, V., additional, Schulte, A., additional, Lamszus, K., additional, Schichor, C., additional, Westphal, M., additional, Tonn, J.-C., additional, Morozova, O., additional, Katzman, S., additional, Grifford, M., additional, Salama, S., additional, Haussler, D., additional, Olshen, A., additional, Fouse, S., additional, Nakamizo, S., additional, Sasayama, T., additional, Tanaka, H., additional, Tanaka, K., additional, Mizukawa, K., additional, Yoshida, M., additional, Kohmura, E., additional, Northcott, P., additional, Jones, D., additional, Pfister, S., additional, Otani, R., additional, Takayanagi, S., additional, Saito, K., additional, Tanaka, S., additional, Shin, M., additional, Ozawa, T., additional, Riester, M., additional, Cheng, Y.-K., additional, Huse, J., additional, Helmy, K., additional, Charles, N., additional, Squatrito, M., additional, Michor, F., additional, Holland, E., additional, Perrech, M., additional, Dreher, L., additional, Rohn, G., additional, Goldbrunner, R., additional, Timmer, M., additional, Pollo, B., additional, Palumbo, V., additional, Calatozzolo, C., additional, Patane, M., additional, Nunziata, R., additional, Farinotti, M., additional, Silvani, A., additional, Lodrini, S., additional, Finocchiaro, G., additional, Lopez, E., additional, Rioscovian, A., additional, Ruiz, R., additional, Siordia, G., additional, de Leon, A. P., additional, Rostomily, C., additional, Rostomily, R., additional, Silbergeld, D., additional, Kolstoe, D., additional, Chamberlain, M., additional, Silber, J., additional, Roth, P., additional, Keller, A., additional, Hoheisel, J., additional, Codo, P., additional, Bauer, A., additional, Backes, C., additional, Leidinger, P., additional, Meese, E., additional, Thiel, E., additional, Korfel, A., additional, Weller, M., additional, Nagae, G., additional, Nagane, M., additional, Sanborn, J. Z., additional, Mikkelsen, T., additional, Jhanwar, S., additional, Chin, L., additional, Nishihara, M., additional, Schliesser, M., additional, Grimm, C., additional, Weiss, E., additional, Claus, R., additional, Weichenhan, D., additional, Weiler, M., additional, Hielscher, T., additional, Sahm, F., additional, Wiestler, B., additional, Klein, A.-C., additional, Blaes, J., additional, Plass, C., additional, Wick, W., additional, Stragliotto, G., additional, Rahbar, A., additional, Soderberg-Naucler, C., additional, Won, M., additional, Ezhilarasan, R., additional, Sun, P., additional, Blumenthal, D., additional, Vogelbaum, M., additional, Jenkins, R., additional, Jeraj, R., additional, Brown, P., additional, Jaeckle, K., additional, Schiff, D., additional, Dignam, J., additional, Atkins, J., additional, Brachman, D., additional, Werner-Wasik, M., additional, Mehta, M., additional, Shen, J., additional, Luan, J., additional, Yu, A., additional, Matsutani, M., additional, Liang, Y., additional, Man, T.-K., additional, Trister, A., additional, Tokita, M., additional, Mikheeva, S., additional, Mikheev, A., additional, Friend, S., additional, van den Bent, M., additional, Erdem, L., additional, Gorlia, T., additional, Taphoorn, M., additional, Kros, J., additional, Wesseling, P., additional, Dubbink, H., additional, Ibdaih, A., additional, French, P., additional, van Thuijl, H., additional, Heimans, J., additional, Ylstra, B., additional, Reijneveld, J., additional, Prabowo, A., additional, Scheinin, I., additional, van Essen, H., additional, Spliet, W., additional, Ferrier, C., additional, van Rijen, P., additional, Veersema, T., additional, Thom, M., additional, Meeteren, A. S.-v., additional, Aronica, E., additional, Kim, H., additional, Zheng, S., additional, Brat, D. J., additional, Virk, S., additional, Amini, S., additional, Sougnez, C., additional, Barnholtz-Sloan, J., additional, Verhaak, R. G. W., additional, Watts, C., additional, Sottoriva, A., additional, Spiteri, I., additional, Piccirillo, S., additional, Touloumis, A., additional, Collins, P., additional, Marioni, J., additional, Curtis, C., additional, Tavare, S., additional, Tews, B., additional, Yeung, T. P. C., additional, Al-Khazraji, B., additional, Morrison, L., additional, Hoffman, L., additional, Jackson, D., additional, Lee, T.-Y., additional, Yartsev, S., additional, Bauman, G., additional, Fu, J., additional, Vegesna, R., additional, Mao, Y., additional, Heathcock, L. E., additional, Torres-Garcia, W., additional, Wang, S., additional, McKenna, A., additional, Brennan, C. W., additional, Yung, W. K. A., additional, Weinstein, J. N., additional, Sulman, E. P., additional, and Koul, D., additional

Published
2013
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15. Genetic risk profiles identify different molecular etiologies for glioma

Author

Simon, M, Hosking, FJ, Marie, Y, Gousias, K, Boisselier, B, Carpentier, C, Schramm, J, Mokhtari, K, Hoang-Xuan, KH, Idbaih, A, Delattre, JY, Lathrop, M, Robertson, LB, Houlston, RS, Sanson, M, Simon, M, Hosking, FJ, Marie, Y, Gousias, K, Boisselier, B, Carpentier, C, Schramm, J, Mokhtari, K, Hoang-Xuan, KH, Idbaih, A, Delattre, JY, Lathrop, M, Robertson, LB, Houlston, RS, and Sanson, M

Published
2010

18. CLIN-PATHOLOGY

Author

Alexandru, D., primary, Satyadev, R., additional, So, W., additional, Lee, S. H., additional, Lee, Y. S., additional, Hong, Y.-K., additional, Kang, C. S., additional, Rodgers, S. D., additional, Marascalchi, B. J., additional, Strom, R. G., additional, Riina, H., additional, Samadani, U., additional, Frempong-Boadu, A., additional, Babu, R., additional, Sen, C., additional, Zagzag, D., additional, Anderson, M. D., additional, Abel, T. W., additional, Moots, P. L., additional, Odia, Y., additional, Orr, B. A., additional, Eberhart, C. G., additional, Rodriguez, F., additional, Sweis, R. T., additional, Lavingia, J., additional, Connelly, J., additional, Cochran, E., additional, van den Bent, M., additional, Hartmann, C., additional, Preusser, M., additional, Strobel, T., additional, Dubbink, H. J., additional, Kros, J. M., additional, von Deimling, A., additional, Boisselier, B., additional, Sanson, M., additional, Halling, K. C., additional, Diefes, K. L., additional, Aldape, K., additional, Giannini, C., additional, Rodriguez, F. J., additional, Ligon, A. H., additional, Horkayne-Szakaly, I., additional, Rushing, E. J., additional, Ligon, K. L., additional, Vena, N., additional, Garcia, D. I., additional, Douglas Cameron, J., additional, Raghunathan, A., additional, Wani, K., additional, Armstrong, T. S., additional, Vera-Bolanos, E., additional, Fouladi, M., additional, Gajjar, A., additional, Goldman, S., additional, Lehman, N. L., additional, Metellus, P., additional, Mikkelsen, T., additional, Necesito-Reyes, M. J. T., additional, Omuro, A., additional, Packer, R. J., additional, Partap, S., additional, Pollack, I. F., additional, Prados, M. D., additional, Ian Robbins, H., additional, Soffietti, R., additional, Wu, J., additional, Gilbert, M. R., additional, Aldape, K. D., additional, Prosniak, M., additional, Harshyne, L. A., additional, Andrews, D. W., additional, Craig Hooper, D., additional, Kagawa, N., additional, Hosen, N., additional, Kijima, N., additional, Hirayama, R., additional, Chiba, Y., additional, Yamamoto, F., additional, Kinoshita, M., additional, Hashimoto, N., additional, Fujimoto, Y., additional, Yoshimine, T., additional, Hu, J., additional, Nuno, M., additional, Patil, C., additional, Rudnick, J., additional, Phuphanich, S., additional, Bannykh, S., additional, Chu, R., additional, Yu, J., additional, Black, K., additional, Choi, J., additional, Kim, D., additional, Shim, K. W., additional, Kim, S. H., additional, Kanno, H., additional, Nishihara, H., additional, Tanaka, S., additional, Yanagi, T., additional, Buczkowicz, P., additional, Khuong-Quang, D.-A., additional, Rakopoulos, P., additional, Bouffet, E., additional, Morrison, A., additional, Bartels, U., additional, Pfister, S. M., additional, Jabado, N., additional, Hawkins, C., additional, Weinberg, B. D., additional, Newell, K. L., additional, Kumar, P., additional, Wang, F., additional, Venneti, S., additional, Madden, M., additional, Coyne, T., additional, Phillips, J., additional, Gorovets, D., additional, Huse, J., additional, Kofler, J., additional, Lu, C., additional, Tihan, T., additional, Sullivan, L., additional, Santi, M., additional, Judkins, A., additional, Thompson, C., additional, Perry, A., additional, Iorgulescu, J. B., additional, Laufer, I., additional, Hameed, M., additional, Lis, E., additional, Boland, P., additional, Komotar, R., additional, Bilsky, M., additional, Amato-Watkins, A. C., additional, Neal, J., additional, Rees, A. D., additional, Davies, J. S., additional, Hayhurst, C., additional, Lu-Emerson, C., additional, Snuderl, M., additional, Davidson, C., additional, Kirkpatrick, N. D., additional, Huang, Y., additional, Duda, D. G., additional, Ancukiewicz, M., additional, Stemmer-Rachamimov, A., additional, Batchelor, T. T., additional, Jain, R. K., additional, Ellezam, B., additional, Theeler, B. J., additional, Sadighi, Z. S., additional, Mehta, V., additional, Tran, M.-D. T., additional, Adesina, A. M., additional, Puduvalli, V. K., additional, and Bruner, J. M., additional

Published
2012
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19. LAB-OMICS AND PROGNOSTIC MARKERS

Author

Jensen, R. L., primary, Abraham, S., additional, Hu, N., additional, Jensen, R. L., additional, Boulay, J.-L., additional, Leu, S., additional, Frank, S., additional, Vassella, E., additional, Vajtai, I., additional, von Felten, S., additional, Taylor, E., additional, Schulz, M., additional, Hutter, G., additional, Sailer, M., additional, Hench, J., additional, Mariani, L., additional, van Thuijl, H. F., additional, Scheinin, I., additional, van Essen, D. F., additional, Heimans, J. J., additional, Wesseling, P., additional, Ylstra, B., additional, Reijneveld, J. C., additional, Borges, A. R., additional, Larrubia, P. L., additional, Marques, J. M. B., additional, Cerdan, S. G., additional, Brastianos, P., additional, Horowitz, P., additional, Santagata, S., additional, Jones, R. T., additional, McKenna, A., additional, Getz, G., additional, Ligon, K., additional, Palescandolo, E., additional, Van Hummelen, P., additional, Stemmer-Rachamimov, A., additional, Louis, D., additional, Hahn, W. C., additional, Dunn, I., additional, Beroukhim, R., additional, Guan, X., additional, Vengoechea, J., additional, Zheng, S., additional, Sloan, A., additional, Chen, Y., additional, Brat, D., additional, O'Neill, B. P., additional, Cohen, M., additional, Aldape, K., additional, Rosenfeld, S., additional, Noushmehr, H., additional, Verhaak, R. G., additional, Barnholtz-Sloan, J., additional, Bahassi, E. M., additional, Li, Y.-Q., additional, Cross, E., additional, Li, W., additional, Vijg, J., additional, McPherson, C., additional, Warnick, R., additional, Stambrook, P., additional, Rixe, O., additional, Manterola, L., additional, Tejada-Solis, S., additional, Diez-Valle, R., additional, Gonzalez, M., additional, Jauregui, P., additional, Sampron, N., additional, Barrena, C., additional, Ruiz, I., additional, Gallego, J., additional, Delattre, J.-Y., additional, de Munain, A. L., additional, Mlonso, M. M., additional, Saito, K., additional, Mukasa, A., additional, Nagae, G., additional, Aihara, K., additional, Takayanagi, S., additional, Aburatani, H., additional, Saito, N., additional, Kong, X.-T., additional, Fu, B. D., additional, Du, S., additional, Hasso, A. N., additional, Linskey, M. E., additional, Bota, D., additional, Li, C., additional, Chen, Y.-S., additional, Chen, Z.-p., additional, Kim, C. H., additional, Cheong, J. H., additional, Kim, J. M., additional, Yelon, N. P., additional, Jacoby, E., additional, Cohen, Z. R., additional, Ishida, J., additional, Kurozumi, K., additional, Ichikawa, T., additional, Onishi, M., additional, Fujii, K., additional, Shimazu, Y., additional, Date, I., additional, Narayanan, R., additional, Ho, Q. H., additional, Levin, B. S., additional, Maeder, M. L., additional, Joung, J. K., additional, Nutt, C. L., additional, Louis, D. N., additional, Thorsteinsdottir, J., additional, Fu, P., additional, Gehrmann, M., additional, Multhoff, G., additional, Tonn, J.-C., additional, Schichor, C., additional, Thirumoorthy, K., additional, Gordon, N., additional, Walston, S., additional, Patel, D., additional, Okamoto, M., additional, Chakravarti, A., additional, Palanichamy, K., additional, French, P., additional, Erdem, L., additional, Gravendeel, L., additional, de Rooi, J., additional, Eilers, P., additional, Idbaih, A., additional, Spliet, W., additional, den Dunnen, W., additional, Teepen, J., additional, Smitt, P. S., additional, Kros, J. M., additional, Gorlia, T., additional, van den Bent, M., additional, McCarthy, D., additional, Cook, R. W., additional, Oelschlager, K., additional, Maetzold, D., additional, Hanna, M., additional, Wick, W., additional, Meisner, C., additional, Hentschel, B., additional, Platten, M., additional, Sabel, M. C., additional, Koeppen, S., additional, Ketter, R., additional, Weiler, M., additional, Tabatabai, G., additional, Schilling, A., additional, von Deimling, A., additional, Gramatzki, D., additional, Westphal, M., additional, Schackert, G., additional, Loeffler, M., additional, Simon, M., additional, Reifenberger, G., additional, Weller, M., additional, Moren, L., additional, Johansson, M., additional, Bergenheim, T., additional, Antti, H., additional, Sulman, E. P., additional, Goodman, L. D., additional, Wani, K. M., additional, DeMonte, F., additional, Aldape, K. D., additional, Krischek, B., additional, Gugel, I., additional, Aref, D., additional, Marshall, C., additional, Croul, S., additional, Zadeh, G., additional, Nilsson, C. L., additional, Sulman, E., additional, Liu, H., additional, Wild, C., additional, Lichti, C. F., additional, Emmett, M. R., additional, Lang, F. F., additional, Conrad, C., additional, Alentorn, A., additional, Marie, Y., additional, Boisselier, B., additional, Carpetier, C., additional, Mokhtari, K., additional, Hoang-Xuan, K., additional, Capelle, L., additional, Lautenschlaeger, T., additional, Huebner, A., additional, McIntyre, J. B., additional, Magliocco, T., additional, Hamilton, M., additional, Easaw, J., additional, Pollo, B., additional, Calatozzolo, C., additional, Vuono, R., additional, Guzzetti, S., additional, Eoli, M., additional, Silvani, A., additional, Di Meco, F., additional, Filippini, G., additional, Finocchiaro, G., additional, Joy, A., additional, Ramesh, A., additional, Smirnov, I., additional, Reiser, M., additional, Shapiro, W., additional, Mills, G., additional, Kim, S., additional, Feuerstein, B., additional, Gonda, D. D., additional, Li, J., additional, McCabe, N., additional, Walker, S., additional, Goffard, N., additional, Wikstrom, K., additional, McLean, E., additional, Greenan, C., additional, Delaney, T., additional, McCarthy, M., additional, McDyer, F., additional, Keating, K. E., additional, James, I. F., additional, Harrison, T., additional, Mullan, P., additional, Harkin, D. P., additional, Carter, B. S., additional, Kennedy, R. D., additional, Chen, C. C., additional, Patel, A. S., additional, Allen, J. E., additional, Dicker, D. T., additional, Rizzo, K., additional, Sheehan, J. M., additional, Glantz, M. J., additional, El-Deiry, W. S., additional, Salhia, B., additional, Ross, J. T., additional, Kiefer, J., additional, Van Cott, C., additional, Metpally, R., additional, Baker, A., additional, Sibenaller, Z., additional, Nasser, S., additional, Ryken, T., additional, Ramanathan, R., additional, Berens, M. E., additional, Carpten, J., additional, Tran, N. L., additional, Bi, Y., additional, Pal, S., additional, Zhang, Z., additional, Gupta, R., additional, Macyszyn, L., additional, Fetting, H., additional, O'Rourke, D., additional, Davuluri, R. V., additional, Ezrin, A. M., additional, Moore, K., additional, Stummer, W., additional, Hadjipanayis, C. G., additional, Cahill, D. P., additional, Beiko, J., additional, Suki, D., additional, Prabhu, S., additional, Weinberg, J., additional, Lang, F., additional, Sawaya, R., additional, Rao, G., additional, McCutcheon, I., additional, Barker, F. G., additional, Trister, A. D., additional, Bot, B., additional, Fontes, K., additional, Bridge, C., additional, Baldock, A. L., additional, Rockhill, J. K., additional, Mrugala, M. M., additional, Rockne, R. R., additional, Huang, E., additional, Swanson, K. R., additional, Underhill, H. R., additional, Zhang, J., additional, Shi, M., additional, Lin, X., additional, Mikheev, A., additional, Rostomily, R. C., additional, Scheck, A. C., additional, Stafford, P., additional, Hughes, A., additional, Cichacz, Z., additional, Coons, S. W., additional, Johnston, S. A., additional, Mainwaring, L., additional, Craig, J., additional, Garcia, D., additional, Bergthold, G., additional, Burns, M., additional, Rich, B., additional, Ramkissoon, S., additional, Eberhart, C., additional, Ligon, A., additional, Goumnerova, L., additional, Stiles, C., additional, Kieran, M., additional, Hahn, W., additional, Olausson, K. H., additional, Correia, J., additional, Gafni, E., additional, Theisen, M., additional, Hayashi, M., additional, Haidar, S., additional, Maire, C., additional, Mainwaring, L. A., additional, Norden, A., additional, Wen, P., additional, Kung, A., additional, Alexander, B., additional, Tonellato, P., additional, and Ligon, K. L., additional

Published
2012
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23. All the 1p19q codeleted gliomas are mutated on IDH1 or IDH2

Author

Labussière, M., primary, Idbaih, A., additional, Wang, X.-W., additional, Marie, Y., additional, Boisselier, B., additional, Falet, C., additional, Paris, S., additional, Laffaire, J., additional, Carpentier, C., additional, Crinière, E., additional, Ducray, F., additional, El Hallani, S., additional, Mokhtari, K., additional, Hoang-Xuan, K., additional, Delattre, J.-Y., additional, and Sanson, M., additional

Published
2010
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26. TP53 codon 72 polymorphism is associated with age at onset of glioblastoma

Author

Hallani, S. E., primary, Ducray, F., additional, Idbaih, A., additional, Marie, Y., additional, Boisselier, B., additional, Colin, C., additional, Laigle-Donadey, F., additional, Rodero, M., additional, Chinot, O., additional, Thillet, J., additional, Hoang-Xuan, K., additional, Delattre, J-Y, additional, and Sanson, M., additional

Published
2009
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30. IDH1or IDH2mutations predict longer survival and response to temozolomide in low-grade gliomas

Author

Houillier, C., Wang, X., Kaloshi, G., Mokhtari, K., Guillevin, R., Laffaire, J., Paris, S., Boisselier, B., Idbaih, A., Laigle-Donadey, F., Hoang-Xuan, K., Sanson, M., and Delattre, J.-Y.

Abstract

Recent studies have shown that IDH1and IDH2mutations occur frequently in gliomas, including low-grade gliomas. However, their impact on the prognosis and chemosensitivity of low-grade gliomas remains unclear.

Published
2010
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31. All the 1p19q codeleted gliomas are mutated on IDH1or IDH2(e–Pub ahead of print)

Author

Labussière, M., Idbaih, A., Wang, X.-W., Marie, Y., Boisselier, B., Falet, C., Paris, S., Laffaire, J., Carpentier, C., Crinière, E., Ducray, F., El Hallani, S., Mokhtari, K., Hoang-Xuan, K., Delattre, J.-Y., and Sanson, M.

Abstract

Recently, the gene encoding the human cytosolic NADPH-dependent isocitrate dehydrogenase (IDH1) was reported frequently mutated in gliomas. Rare mutations were also found in the sequence of the mitochondrial isoform IDH2.

Published
2010
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33. Correction: ASPM-associated stem cell proliferation is involved in malignant progression of gliomas and constitutes an attractive therapeutic target

Author

Calvo Charles, Boisselier Blandine, Idbaih Ahmed, Rousseau Audrey, Ravassard Philippe, Vampouille Raphaël, Marie Yannick, Colin Carole, Bikeye Sandra-Nadia, Leuraud Pascal, Lassalle Myriam, El Hallani Soufiane, Delattre Jean-Yves, and Sanson Marc

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282, Cytology, QH573-671
Published
2011
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34. ASPM-associated stem cell proliferation is involved in malignant progression of gliomas and constitutes an attractive therapeutic target

Author

Calvo Charles, Boisselier Blandine, Idbaih Ahmed, Rousseau Audrey, Ravassard Philippe, Vampouille Raphaël, Marie Yannick, Colin Carole, Bikeye Sandra-Nadia, Leuraud Pascal, Lassalle Myriam, El Hallani Soufiane, Delattre Jean-Yves, and Sanson Marc

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282, Cytology, QH573-671
Abstract

Abstract Background ASPM (Abnormal Spindle-like Microcephaly associated) over-expression was recently implicated in the development of malignant gliomas. Results To better characterize the involvement of ASPM in gliomas, we investigated the mRNA expression in 175 samples, including 8 WHO Grade II, 75 WHO Grade III and 92 WHO Grade IV tumors. Aspm expression was strongly correlated with tumor grade and increased at recurrence when compared to the initial lesion, whatever the initial grade of the primary tumor. ASPM expression also increased over serial passages in gliomaspheres in vitro and in mouse xenografts in vivo. Lentivirus-mediated shRNA silencing of ASPM resulted in dramatic proliferation arrest and cell death in two different gliomasphere models. Conclusion These data suggest that ASPM is involved in the malignant progression of gliomas, possibly through expansion of a cancer stem cell compartment, and is an attractive therapeutic target in glioblastoma multiforme.

Published
2010
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35. Detection, characterization and inhibition of FGFR-TACC fusions in IDH wild type glioma

Author

Josep Tabernero, Jennifer A. Chan, Blandine Boisselier, Julien Savatovsky, Kevin Petrecca, Anna Lasorella, Aurélie Kamoun, Gaetano Finocchiaro, Hayat Belaid, Alessandra Fucci, Antonio Iavarone, Mehdi Touat, Feng R. Luo, Yannick Marie, Anna Luisa Di Stefano, Marc Sanson, Rosina Paterra, Marica Eoli, Marine Giry, Stephen Yip, Karima Mokhtari, Jean-Charles Soria, Ahmed Idbaih, Veronique Frattini, Aurelie Bruno, Caroline Houillier, Marianne Labussière, Pietro Zoppoli, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), Service de neurologie 2 [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Dpt of Brain and Behavioral Sciences [Pavia], University of Pavia, Institute for Cancer Genetics, Columbia University Irving Medical Center (CUIMC), Laboratoire de Neuropathologie Raymond Escourolle, Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Università degli Studi di Pavia = University of Pavia (UNIPV), Laboratoire de Neuropathologie Raymond Escourolle [CHU Pitié-Salpétriêre], Université Pierre et Marie Curie - Paris 6 (UPMC)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Di Stefano, Al, Fucci, A, Frattini, V, Labussiere, M, Mokhtari, K, Zoppoli, P, Marie, Y, Bruno, A, Boisselier, B, Giry, M, Savatovsky, J, Touat, M, Belaid, H, Kamoun, A, Idbaih, A, Houillier, C, Luo, Fr, Soria, Jc, Tabernero, J, Eoli, M, Paterra, R, Yip, S, Petrecca, K, Chan, Ja, Finocchiaro, G, Lasorella, A, Sanson, M, and Iavarone, A.

Subjects
musculoskeletal diseases, Male, Cancer Research, IDH1, Oncogene Proteins, Fusion, FGFR Inhibition, DNA Mutational Analysis, Fluorescent Antibody Technique, Mice, Nude, [SDV.CAN]Life Sciences [q-bio]/Cancer, Antineoplastic Agents, Kaplan-Meier Estimate, Biology, Article, Mice, Glioma, Quinoxalines, medicine, Receptor, Fibroblast Growth Factor, Type 3, Animals, Humans, Molecular Targeted Therapy, Reverse Transcriptase Polymerase Chain Reaction, Brain Neoplasms, Wild type, medicine.disease, Fusion protein, Molecular biology, Immunohistochemistry, Xenograft Model Antitumor Assays, Isocitrate Dehydrogenase, 3. Good health, Oncology, Fibroblast growth factor receptor, Pyrazoles, Female, Microtubule-Associated Proteins, Immunostaining
Abstract

Purpose: Oncogenic fusions consisting of fibroblast growth factor receptor (FGFR) and TACC are present in a subgroup of glioblastoma (GBM) and other human cancers and have been proposed as new therapeutic targets. We analyzed frequency and molecular features of FGFR–TACC fusions and explored the therapeutic efficacy of inhibiting FGFR kinase in GBM and grade II and III glioma. Experimental Design: Overall, 795 gliomas (584 GBM, 85 grades II and III with wild-type and 126 with IDH1/2 mutation) were screened for FGFR–TACC breakpoints and associated molecular profile. We also analyzed expression of the FGFR3 and TACC3 components of the fusions. The effects of the specific FGFR inhibitor JNJ-42756493 for FGFR3–TACC3–positive glioma were determined in preclinical experiments. Two patients with advanced FGFR3–TACC3–positive GBM received JNJ-42756493 and were assessed for therapeutic response. Results: Three of 85 IDH1/2 wild-type (3.5%) but none of 126 IDH1/2-mutant grade II and III gliomas harbored FGFR3–TACC3 fusions. FGFR–TACC rearrangements were present in 17 of 584 GBM (2.9%). FGFR3–TACC3 fusions were associated with strong and homogeneous FGFR3 immunostaining. They are mutually exclusive with IDH1/2 mutations and EGFR amplification, whereas they co-occur with CDK4 amplification. JNJ-42756493 inhibited growth of glioma cells harboring FGFR3–TACC3 in vitro and in vivo. The two patients with FGFR3–TACC3 rearrangements who received JNJ-42756493 manifested clinical improvement with stable disease and minor response, respectively. Conclusions: RT-PCR sequencing is a sensitive and specific method to identify FGFR–TACC–positive patients. FGFR3–TACC3 fusions are associated with uniform intratumor expression of the fusion protein. The clinical response observed in the FGFR3–TACC3–positive patients treated with an FGFR inhibitor supports clinical studies of FGFR inhibition in FGFR–TACC–positive patients. Clin Cancer Res; 21(14); 3307–17. ©2015 AACR. See related commentary by Ahluwalia and Rich, p. 3105

Published
2015

36. Mitochondrial DNA copy number as a prognostic marker is age-dependent in adult glioblastoma.

Author

Sourty B, Dardaud LM, Bris C, Desquiret-Dumas V, Boisselier B, Basset L, Figarella-Branger D, Morel A, Sanson M, Procaccio V, and Rousseau A

Abstract

Background: Glioblastoma (GBM) is the most common and aggressive form of glioma. GBM frequently displays chromosome (chr) 7 gain, chr 10 loss and/or EGFR amplification (chr7+/chr10-/ EGFR amp). Overall survival (OS) is 15 months after treatment. In young adults, IDH1/2 mutations are associated with longer survival. In children, histone H3 mutations portend a dismal prognosis. Novel reliable prognostic markers are needed in GBM. We assessed the prognostic value of mitochondrial DNA (mtDNA) copy number in adult GBM., Methods: mtDNA copy number was assessed using real-time quantitative PCR in 232 primary GBM. Methylation of POLG and TFAM genes, involved in mtDNA replication, was assessed by bisulfite-pyrosequencing in 44 and 51 cases, respectively., Results: Median age at diagnosis was 56.6 years-old and median OS, 13.3 months. 153/232 GBM (66 %) displayed chr7+/chr10-/ EGFR amp, 23 (9.9 %) IDH1/2 mutation, 3 (1.3 %) H3 mutation and 53 (22.8 %) no key genetic alterations. GBM were divided into two groups, "Low" ( n = 116) and "High" ( n = 116), according to the median mtDNA/nuclear DNA ratio (237.7). There was no significant difference in OS between the two groups. By dividing the whole cohort according to the median age at diagnosis, OS was longer in the "High" vs "Low" subgroup (27.3 vs 15 months, P = .0203) in young adult GBM ( n = 117) and longer in the "Low" vs "High" subgroup (14.5 vs 10.2 months, P = .0116) in older adult GBM ( n = 115). POLG was highly methylated, whereas TFAM remained unmethylated., Conclusion: mtDNA copy number may be a novel prognostic biomarker in GBM, its impact depending on age., (© The Author(s) 2022. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

Published
2022
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37. RNA-sequencing of IDH-wild-type glioblastoma with chromothripsis identifies novel gene fusions with potential oncogenic properties.

Author

Ah-Pine F, Casas D, Menei P, Boisselier B, Garcion E, and Rousseau A

Abstract

Glioblastoma (GBM) is the most frequent and most aggressive form of glioma. It is characterized by marked genomic instability, which suggests that chromothripsis (CT) might be involved in GBM initiation. Recently, CT has emerged as an alternative mechanism of cancer development, involving massive chromosome rearrangements in a one-step catastrophic event. The aim of the study was to detect CT in GBM and identify novel gene fusions in CT regions. One hundred and seventy IDH-wild-type GBM were screened for CT patterns using whole-genome single nucleotide polymorphism (SNP) arrays. RNA sequencing was performed in 52 GBM with CT features to identify gene fusions within CT regions. Forty tumors (40/52, 77%) harbored at least one gene fusion within CT regions. We identified 120 candidate gene fusions, 30 of which with potential oncogenic activities. We validated 11 gene fusions, which involved the most recurrent fusion partners (EGFR, SEPT14, VOPP1 and CPM), by RT-PCR and Sanger sequencing. The occurrence of CT points to underlying gene fusions in IDH-wild-type GBM. CT provides exciting new research avenues in this highly aggressive cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Published
2021
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39. Whole genome duplication is an early event leading to aneuploidy in IDH -wild type glioblastoma.

Author

Boisselier B, Dugay F, Belaud-Rotureau MA, Coutolleau A, Garcion E, Menei P, Guardiola P, and Rousseau A

Abstract

Glioblastoma, the most frequent and lethal form of glioma, displays chromosome instability and recurrent somatic copy number alterations (SCNA). Chromothripsis and whole genome duplication (WGD) have been recently identified in cancer. In the present study, we analyzed SCNA and determine the ploidy pattern in 123 IDH -wild-type glioblastomas, using SNP array data. WGD and chromothripsis events were validated using, respectively, FISH and CTLPScanner. WGD was detected in 11.4% glioblastomas (14/123) and was associated with TP53 mutation ( p = 0.0068). It was an early event occurring after the recurrent SCNA observed in diffuse high-grade gliomas. Glioblastomas with WGD were more aneuploid compared to glioblastomas without WGD ( p < 0.0001). Chromothripsis occurred in 29.3% glioblastomas (36/123) and mostly affected chromosomes 7, 9 and 12, with amplification of oncogenes (EGFR, MDM2 / CDK4 ), and homozygous deletion of tumor suppressor genes ( CDKN2A ). There was a significant association between chromothripsis and gene rearrangement at a given locus. WGD is an early genetic event significantly associated to TP53 mutation and leading to chromosome instability and aneuploidy in IDH -wild-type glioblastoma. Chromothripsis recurrently targets oncogenes and tumor suppressor genes that are key players in gliomagenesis and tumor progression. The occurrence of chromothripsis points to underlying gene rearrangements (including gene fusions), potential therapeutic targets in glioblastoma., Competing Interests: CONFLICTS OF INTEREST Authors declare no conflicts of interest.

Published
2018
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40. Identification of novel recurrent ETV6-IgH fusions in primary central nervous system lymphoma.

Author

Bruno A, Labreche K, Daniau M, Boisselier B, Gauchotte G, Royer-Perron L, Rahimian A, Lemoine F, de la Grange P, Guégan J, Bielle F, Polivka M, Adam C, Meyronet D, Figarella-Branger D, Villa C, Chrétien F, Eimer S, Davi F, Rousseau A, Houillier C, Soussain C, Mokhtari K, Hoang-Xuan K, and Alentorn A

Subjects
Central Nervous System Neoplasms pathology, Female, Follow-Up Studies, Humans, Lymphoma, Large B-Cell, Diffuse pathology, Male, Middle Aged, Prognosis, Survival Rate, ETS Translocation Variant 6 Protein, Biomarkers, Tumor genetics, Central Nervous System Neoplasms genetics, Immunoglobulin Heavy Chains genetics, Lymphoma, Large B-Cell, Diffuse genetics, Oncogene Proteins, Fusion genetics, Proto-Oncogene Proteins c-ets genetics, Repressor Proteins genetics
Abstract

Background: Primary central nervous system lymphoma (PCNSL) represents a particular entity within non-Hodgkin lymphomas and is associated with poor outcome. The present study addresses the potential clinical relevance of chimeric transcripts in PCNSL discovered by using RNA sequencing (RNA-seq)., Methods: Seventy-two immunocompetent and newly diagnosed PCNSL cases were included in the present study. Among them, 6 were analyzed by RNA-seq to detect new potential fusion transcripts. We confirmed the results in the remaining 66 PCNSL. The gene fusion was validated by fluorescence in situ hybridization (FISH) using formalin-fixed paraffin-embedded (FFPE) samples. We assessed the biological and clinical impact of one new gene fusion., Results: We identified a novel recurrent gene fusion, E26 transformation-specific translocation variant 6-immunoglobulin heavy chain (ETV6-IgH). Overall, ETV6-IgH was found in 13 out of 72 PCNSL (18%). No fusion conserved an intact functional domain of ETV6, and ETV6 was significantly underexpressed at gene level, suggesting an ETV6 haploinsufficiency mechanism. The presence of the gene fusion was also validated by FISH in FFPE samples. Finally, PCNSL samples harboring ETV6-IgH showed a better prognosis in multivariate analysis, P = 0.03, hazard ratio = 0.33, 95% CI = 0.12-0.88. The overall survival at 5 years was 69% for PCNSL harboring ETV6-IgH versus 29% for samples without this gene fusion., Conclusions: ETV6-IgH is a new potential surrogate marker of PCNSL with favorable prognosis with ETV6 haploinsufficiency as a possible mechanism. The potential clinical impact of ETV6-IgH should be validated in larger prospective studies.

Published
2018
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41. Molecular alterations in pediatric gliomatosis cerebri are similar to those in less invasive forms of pediatric diffuse glioma.

Author

Boisselier B, De Carli E, and Rousseau A

Subjects
Brain Neoplasms mortality, Brain Neoplasms pathology, Child, Child, Preschool, Female, Glioma mortality, Glioma pathology, Humans, Male, Neoplasm Invasiveness genetics, Retrospective Studies, Brain Neoplasms genetics, Brain Neoplasms metabolism, Glioma genetics, Glioma metabolism
Published
2017
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42. BRAF-V600E immunohistochemistry in a large series of glial and glial-neuronal tumors.

Author

Breton Q, Plouhinec H, Prunier-Mirebeau D, Boisselier B, Michalak S, Menei P, and Rousseau A

Subjects
Adolescent, Adult, Aged, Central Nervous System Neoplasms genetics, Child, Child, Preschool, Female, Glioma genetics, Humans, Immunohistochemistry methods, Infant, Male, Middle Aged, Mutation, Real-Time Polymerase Chain Reaction, Sensitivity and Specificity, Sequence Analysis, DNA methods, Young Adult, Central Nervous System Neoplasms diagnosis, Glioma diagnosis, Immunohistochemistry standards, Proto-Oncogene Proteins B-raf genetics, Sequence Analysis, DNA standards
Abstract

Introduction: Some glial-neuronal tumors (GNT) (pleomorphic xantho-astrocytoma [PXA], ganglioglioma [GG]) display BRAF-V600E mutation, which represents a diagnostic clue to these entities. Targeted therapies against BRAF-V600 protein have shown promising results in GNT. The aim of this study was to assess the utility of BRAF-V600E immunohistochemistry (IHC, clone VE1) in daily practice in a series of 140 glial, and GNT compared to molecular biology (MB) techniques., Methods: We performed BRAF-V600E IHC on all 140 cases. We used Sanger sequencing and allele-specific quantitative PCR (ASQ-PCR) to detect BRAF-V600E mutation when sufficient amount of materiel was available., Results: BRAF-V600E immunostaining was detected in 29.5% of cases (41/140 cases; 61.5% GG/GC/AGG (32/52), 33% PXA, 6.6% pilocytic astrocytomas). In 47 cases, MB could be performed: Sanger sequencing and ASQ-PCR in 34 cases, ASQ-PCR only in 11 cases, and Sanger sequencing only in two cases. In initial tumors, Sanger sequencing identified BRAF-V600E mutation in 19.5% tumors (seven of 36 tested cases). ASQ-PCR showed mutation in 48.5% tumors (17/35 tested cases). In six cases (5 GG, one PXA), the results were discordant between IHC and MB; the five GG cases were immunopositive for BRAF-V600E but wild type with both MB techniques. In another 7 GG, the percentage of mutated (ganglion) cells was low, and Sanger sequencing failed to detect the mutation, which was detected by IHC and ASQ-PCR., Conclusions: In tumors with few mutated cells (e.g., GG), anti-BRAF-V600E IHC appears more sensitive than Sanger sequencing. The latter, although considered as the gold standard, is not to be used up-front to detect BRAF mutation in GG. The combination of IHC and ASQ-PCR appears more efficient to appraise the indication of targeted therapies in these glioneuronal tumors.

Published
2017
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43. Chromosome 17p Homodisomy Is Associated With Better Outcome in 1p19q Non-Codeleted and IDH-Mutated Gliomas.

Author

Labussière M, Rahimian A, Giry M, Boisselier B, Schmitt Y, Polivka M, Mokhtari K, Delattre JY, Idbaih A, Labreche K, Alentorn A, and Sanson M

Subjects
Adult, Aged, Biomarkers, Tumor genetics, Chromosomes, Human, Pair 17 genetics, Disease-Free Survival, Female, Glioma epidemiology, Glioma pathology, Humans, Male, Middle Aged, Mutation, Prognosis, Glioma genetics, Isocitrate Dehydrogenase genetics, Loss of Heterozygosity genetics, Tumor Suppressor Protein p53 genetics
Abstract

Background: The 1p19q non-codeleted gliomas with IDH mutation, defined as "molecular astrocytomas," display frequent TP53 mutations and have an intermediate prognosis. We investigated the prognostic impact of copy number-neutral loss of heterozygosity (CNLOH) in 17p in this population., Methods: We analyzed 793 gliomas (206 grade II, 377 grade III, and 210 grade IV) by single nucleotide polymorphism array and for TP53 mutations., Results: Homodisomy revealed by CNLOH was observed in 156 cases (19.7%). It was more frequent in astrocytomas and oligoastrocytomas (98/256, 38%) than oligodendrogliomas (28/327, 8.6%; p < .0001) or glioblastoma multiforme (30/210, 14.3%; p < .0001), tightly associated with TP53 mutation (69/71 vs. 20/79; p = 2 × 10(-16)), and mutually exclusive with 1p19q codeletion (1/156 vs. 249/556; p < .0001). In the group of IDH-mutated 1p19q non-codeleted gliomas, CNLOH 17p was associated with longer survival (86.3 vs. 46.2 months; p = .004), particularly in grade III gliomas (overall survival >100 vs. 37.9 months; p = .007). These data were confirmed in an independent dataset from the Cancer Genome Atlas., Conclusion: CNLOH 17p is a prognostic marker and further refines the molecular classification of gliomas., Implications for Practice: Homodisomy of chromosome 17p (CNLOH 17p) is a frequent feature in IDH-mutated 1p19q non-codeleted gliomas (group 2). It is constantly associated with TP53 mutation. It was found, within this specific molecular group of gliomas (corresponding to molecular astrocytomas), that CNLOH 17p is associated with a much better outcome and may therefore represent an additional prognostic marker to refine the prognostic classification of gliomas., Competing Interests: of potential conflicts of interest may be found at the end of this article., (©AlphaMed Press.)

Published
2016
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44. Severe hydrocephalus caused by diffuse leptomeningeal and neurocutaneous melanocytosis of antenatal onset: a clinical, pathologic, and molecular study of 2 cases.

Author

Uguen A, Laurent C, Samaison L, Boisselier B, Talagas M, Costa S, Aziza J, Mokhtari K, Le Maréchal C, and Marcorelles P

Subjects
Comparative Genomic Hybridization, Female, Fetus, High-Throughput Nucleotide Sequencing, Humans, In Situ Hybridization, Fluorescence, Melanosis complications, Melanosis genetics, Neurocutaneous Syndromes complications, Neurocutaneous Syndromes genetics, Pregnancy, Hydrocephalus etiology, Melanosis pathology, Meninges pathology, Neurocutaneous Syndromes pathology
Abstract

Diffuse leptomeningeal melanocytosis (DLM) is a rare nevomelanocytic proliferation arising in the meninges. Despite their lack of morphological features of malignancy, these clonal nevomelanocytic cells are capable of extensive invasion and of malignant behavior. When associated with congenital melanocytic nevi, the disorder is named neurocutaneous melanocytosis (NCM). When symptomatic, DLM is usually revealed during childhood, but some cases remain clinically silent. The aim of this study was to analyze melanocytic proliferation in 2 rare and severe cases of isolated DLM and NCM of prenatal onset by neuropathologic and molecular analysis. We performed neuropathologic examination, comparative genomic hybridization arrays, fluorescence in situ hybridization, BRAF and NRAS pyrosequencing in the 2 cases, and next-generation sequencing in the case of isolated DLM. The neuropathologic examination showed diffuse meningeal melanocytic proliferation involving the whole central nervous system with multiple areas of intraneural invasion, associated with large nevi in 1 case. We did not find any chromosomal imbalances. A NRAS(Q61K) mutation was found in the cutaneous and meningeal lesions from the NCM. No mutation was found within a panel of oncogenes including BRAF, NRAS, HRAS, KIT, GNAQ, and GNA11 concerning the isolated DLM. We report 2 exceptional cases of hydrocephalus of prenatal onset related to DLM and NCM. The molecular mechanisms underlying our case of DLM remain unsolved despite the panel of analysis applied., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Published
2015
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45. Detection, Characterization, and Inhibition of FGFR-TACC Fusions in IDH Wild-type Glioma.

Author

Di Stefano AL, Fucci A, Frattini V, Labussiere M, Mokhtari K, Zoppoli P, Marie Y, Bruno A, Boisselier B, Giry M, Savatovsky J, Touat M, Belaid H, Kamoun A, Idbaih A, Houillier C, Luo FR, Soria JC, Tabernero J, Eoli M, Paterra R, Yip S, Petrecca K, Chan JA, Finocchiaro G, Lasorella A, Sanson M, and Iavarone A

Subjects
Animals, Brain Neoplasms drug therapy, Brain Neoplasms mortality, DNA Mutational Analysis methods, Female, Fluorescent Antibody Technique, Glioma drug therapy, Glioma mortality, Humans, Immunohistochemistry, Isocitrate Dehydrogenase genetics, Kaplan-Meier Estimate, Male, Mice, Mice, Nude, Microtubule-Associated Proteins genetics, Molecular Targeted Therapy, Receptor, Fibroblast Growth Factor, Type 3 genetics, Reverse Transcriptase Polymerase Chain Reaction methods, Xenograft Model Antitumor Assays, Antineoplastic Agents therapeutic use, Brain Neoplasms genetics, Glioma genetics, Oncogene Proteins, Fusion genetics, Pyrazoles therapeutic use, Quinoxalines therapeutic use
Abstract

Purpose: Oncogenic fusions consisting of fibroblast growth factor receptor (FGFR) and TACC are present in a subgroup of glioblastoma (GBM) and other human cancers and have been proposed as new therapeutic targets. We analyzed frequency and molecular features of FGFR-TACC fusions and explored the therapeutic efficacy of inhibiting FGFR kinase in GBM and grade II and III glioma., Experimental Design: Overall, 795 gliomas (584 GBM, 85 grades II and III with wild-type and 126 with IDH1/2 mutation) were screened for FGFR-TACC breakpoints and associated molecular profile. We also analyzed expression of the FGFR3 and TACC3 components of the fusions. The effects of the specific FGFR inhibitor JNJ-42756493 for FGFR3-TACC3-positive glioma were determined in preclinical experiments. Two patients with advanced FGFR3-TACC3-positive GBM received JNJ-42756493 and were assessed for therapeutic response., Results: Three of 85 IDH1/2 wild-type (3.5%) but none of 126 IDH1/2-mutant grade II and III gliomas harbored FGFR3-TACC3 fusions. FGFR-TACC rearrangements were present in 17 of 584 GBM (2.9%). FGFR3-TACC3 fusions were associated with strong and homogeneous FGFR3 immunostaining. They are mutually exclusive with IDH1/2 mutations and EGFR amplification, whereas they co-occur with CDK4 amplification. JNJ-42756493 inhibited growth of glioma cells harboring FGFR3-TACC3 in vitro and in vivo. The two patients with FGFR3-TACC3 rearrangements who received JNJ-42756493 manifested clinical improvement with stable disease and minor response, respectively., Conclusions: RT-PCR sequencing is a sensitive and specific method to identify FGFR-TACC-positive patients. FGFR3-TACC3 fusions are associated with uniform intratumor expression of the fusion protein. The clinical response observed in the FGFR3-TACC3-positive patients treated with an FGFR inhibitor supports clinical studies of FGFR inhibition in FGFR-TACC-positive patients., (©2015 American Association for Cancer Research.)

Published
2015
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46. VEGFA SNP rs2010963 is associated with vascular toxicity in recurrent glioblastomas and longer response to bevacizumab.

Author

Di Stefano AL, Labussiere M, Lombardi G, Eoli M, Bianchessi D, Pasqualetti F, Farina P, Cuzzubbo S, Gallego-Perez-Larraya J, Boisselier B, Ducray F, Cheneau C, Moglia A, Finocchiaro G, Marie Y, Rahimian A, Hoang-Xuan K, Delattre JY, Mokhtari K, and Sanson M

Subjects
Bevacizumab, Brain Neoplasms blood, Brain Neoplasms mortality, Disease-Free Survival, Enzyme-Linked Immunosorbent Assay, Genotype, Glioblastoma blood, Glioblastoma mortality, Hemorrhage chemically induced, Hemorrhage epidemiology, Hemorrhage genetics, Humans, Kaplan-Meier Estimate, Neoplasm Recurrence, Local drug therapy, Neoplasm Recurrence, Local genetics, Thrombosis chemically induced, Thrombosis epidemiology, Thrombosis genetics, Vascular Endothelial Growth Factor A blood, Angiogenesis Inhibitors adverse effects, Antibodies, Monoclonal, Humanized adverse effects, Brain Neoplasms drug therapy, Glioblastoma drug therapy, Polymorphism, Single Nucleotide, Vascular Endothelial Growth Factor A genetics
Abstract

Although anti-VEGF therapy is widely used in high-grade gliomas, no predictor of response or toxicity has been reported yet. We investigated here the association of the functional single nucleotide polymorphism (SNP) rs2010963, located in the 5' untranslated terminal region of the VEGFA gene, with survival, response to bevacizumab (BVZ) and vascular toxicity. The rs2010963 was genotyped by Taqman assay in blood DNA from 954 glioma patients with available survival data, including 225 glioblastoma (GBM) patients treated with BVZ. VEGFA plasma levels were assessed by ELISA in 87 patients before treatment. Thrombo-hemorragic adverse events were recorded during BVZ treatment or not, and in an independent population of 92 GBM patients treated with temozolomide. The CC genotype was associated with the occurrence of thrombo-hemorragic events (CC 25 versus CG 13.5 and GG 5.2 %; P = 0.0044) during BVZ. A similar but weaker and non significant trend was observed in patients not receiving BVZ. A CC genotype was associated with higher levels of plasma VEGFA at baseline (107.6 versus 57.50 pg/mL in heterozygotes (CG) and 52.75 pg/mL in GG patients, P = 0.035 and P = 0.028 respectively). The CC genotype tended to be associated to longer PFS when treated with BVZ (P = 0.05), but not when treated with the temozolomide treatment. Our data suggest that the rs2010963 genotype is associated with longer PFS, higher risk of vascular events in recurrent GBM especially treated with BVZ, and higher plasma VEGFA concentration. It may help to identify patients at risk of vascular adverse events during BVZ treatment.

Published
2015
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47. Combined analysis of TERT, EGFR, and IDH status defines distinct prognostic glioblastoma classes.

Author

Labussière M, Boisselier B, Mokhtari K, Di Stefano AL, Rahimian A, Rossetto M, Ciccarino P, Saulnier O, Paterra R, Marie Y, Finocchiaro G, and Sanson M

Subjects
Adolescent, Adult, Aged, Aged, 80 and over, Brain Neoplasms mortality, Brain Neoplasms pathology, DNA Modification Methylases genetics, Female, Glioblastoma mortality, Glioblastoma pathology, Humans, Male, Middle Aged, Prognosis, Young Adult, Brain Neoplasms genetics, ErbB Receptors genetics, Glioblastoma genetics, Isocitrate Dehydrogenase genetics, Mutation genetics, Telomerase genetics
Abstract

Objective: To identify the prognostic significance of TERT promoter mutations (TERTp-mut) and their associations with common molecular alterations in glioblastomas (GBMs)., Methods: We sequenced the TERTp-mut in DNA from 395 GBMs and analyzed the results with their respective histology, genetic profile (IDH1 mutation, EGFR amplification, CDKN2A homozygous deletion, loss of chromosome 10, TP53 mutation), and overall survival (OS)., Results: TERTp-mut were found in 299 of 395 GBMs (75.7%) and were associated with an older age (median 59.6 years for TERTp-mut vs 53.6 years for TERT promoter wild type [TERTp-wt], p < 0.0001). TERTp-mut was an independent factor of poor prognosis (OS = 13.8 vs 18.4 months), in both IDH-mutated (OS = 13.8 vs 37.6 months, p = 0.022) and IDH-wt GBMs (OS = 13.7 vs 17.5 months, p = 0.006). TERTp-mut was associated with IDH-wt, EGFR amplification, CDKN2A deletion, and chromosome 10q loss, but not with MGMT promoter methylation. In the TERTp-wt group, OS was twice longer in EGFR-wt than in EGFR amplification GBMs (OS = 26.6 vs 13.3 months; p = 0.005). In the EGFR-wt group, patients with TERTp-wt had a significantly better outcome (OS = 26.3 vs 12.5 months, p < 0.0001), whereas in the EGFR amplification group, patients with TERTp-mut survived longer (OS = 15.8 vs 13.3 months, p = 0.05). Taken together, the absence of both EGFR amplification and TERTp-mut is associated with longer survival in patients with GBM (26.5 months for patients with IDH-wt, 36.7 months for patients with IDH mutation)., Conclusions: The analysis of TERTp-mut, in combination with EGFR amplification and IDH mutation status, refines the prognostic classification of GBMs., (© 2014 American Academy of Neurology.)

Published
2014
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48. Mutational analysis of primary central nervous system lymphoma.

Author

Bruno A, Boisselier B, Labreche K, Marie Y, Polivka M, Jouvet A, Adam C, Figarella-Branger D, Miquel C, Eimer S, Houillier C, Soussain C, Mokhtari K, Daveau R, and Hoang-Xuan K

Subjects
B-Lymphocytes metabolism, B-Lymphocytes pathology, DNA Mutational Analysis methods, Humans, INDEL Mutation, Polymorphism, Single Nucleotide, Central Nervous System Neoplasms genetics, Exome genetics, Genetic Predisposition to Disease genetics, Lymphoma, Large B-Cell, Diffuse genetics, Mutation
Abstract

Little is known about the genomic basis of primary central nervous system lymphoma (PCNSL) tumorigenesis. To investigate the mutational profile of PCNSL, we analyzed nine paired tumor and germline DNA samples from PCNSL patients by high throughput exome sequencing. Eight genes of interest have been further investigated by focused resequencing in 28 additional PCNSL tumors to better estimate their incidence. Our study identified recurrent somatic mutations in 37 genes, some involved in key signaling pathways such as NFKB, B cell differentiation and cell cycle control. Focused resequencing in the larger cohort revealed high mutation rates for genes already described as mutated in PCNSL such as MYD88 (38%), CD79B (30%), PIM1 (22%) and TBL1XR1 (19%) and for genes not previously reported to be involved in PCNSL tumorigenesis such as ETV6 (16%), IRF4 (14%), IRF2BP2 (11%) and EBF1 (11%). Of note, only 3 somatically acquired SNVs were annotated in the COSMIC database. Our results demonstrate a high genetic heterogeneity of PCNSL and mutational pattern similarities with extracerebral diffuse large B cell lymphomas, particularly of the activated B-cell (ABC) subtype, suggesting shared underlying biological mechanisms. The present study provides new insights into the mutational profile of PCNSL and potential targets for therapeutic strategies.

Published
2014
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49. A new sensitive PCR assay for one-step detection of 12 IDH1/2 mutations in glioma.

Author

Catteau A, Girardi H, Monville F, Poggionovo C, Carpentier S, Frayssinet V, Voss J, Jenkins R, Boisselier B, Mokhtari K, Sanson M, Peyro-Saint-Paul H, and Giannini C

Subjects
Adolescent, Brain Neoplasms genetics, Child, Datasets as Topic, Female, Glioma genetics, Humans, Male, Reproducibility of Results, Retrospective Studies, Sensitivity and Specificity, Young Adult, Brain Neoplasms diagnosis, Glioma diagnosis, Isocitrate Dehydrogenase genetics, Mutation genetics, Polymerase Chain Reaction methods
Abstract

Introduction: Mutations in isocitrate dehydrogenase genes IDH1 or IDH2 are frequent in glioma, and IDH mutation status is a strong diagnostic and prognostic marker. Current IDH mutation screening is performed with an immunohistochemistry (IHC) assay specific for IDH1 R132H, the most common mutation. Sequencing is recommended as a second-step test for IHC-negative or -equivocal cases. We developed and validated a new real-time quantitative polymerase chain reaction (PCR) assay for single-step detection of IDH1 R132H and 11 rare IDH1/2 mutations in formalin-fixed paraffin-embedded (FFPE) glioma samples. Performance of the IDH1/2 PCR assay was compared to IHC and Sanger sequencing., Results: The IDH1/2 PCR assay combines PCR clamping for detection of 7 IDH1 and 5 IDH2 mutations, and Amplification Refractory Mutation System technology for specific identification of the 3 most common mutations (IDH1 R132H, IDH1 R132C, IDH2 R172K). Analytical sensitivity of the PCR assay for mutation detection was <5% for 11/12 mutations (mean: 3.3%), and sensitivity for mutation identification was very high (0.8% for IDH1 R132H; 1.2% for IDH1 R132C; 0.6% for IDH2 R172K). Assay performance was further validated on 171 clinical glioma FFPE samples; of these, 147 samples met the selection criteria and 146 DNA samples were successfully extracted. IDH1/2 status was successfully obtained in 91% of cases. All but one positive IDH1 R132H-IHC cases were concordantly detected by PCR and 3 were not detected by sequencing. Among the IHC-negative cases (n = 72), PCR detected 12 additional rare mutations (10 IDH1, 2 IDH2). All mutations detected by sequencing (n = 67) were concordantly detected by PCR and 5/66 sequencing-negative cases were PCR-positive (overall concordance: 96%). Analysis of synthetic samples representative of the 11 rare IDH1/2 mutations detected by the assay produced 100% correct results., Conclusions: The new IDH1/2 PCR assay has a high technical success rate and is more sensitive than Sanger sequencing. Positive concordance was 98% with IHC for IDH1 R132H detection and 100% with sequencing. The PCR assay can reliably be performed on FFPE samples and has a faster turnaround time than current IDH mutation detection algorithms. The assay should facilitate implementation of a comprehensive IDH1/2 testing protocol in routine clinical practice.

Published
2014
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50. Clinical value of chromosome arms 19q and 11p losses in low-grade gliomas.

Author

Alentorn A, van Thuijl HF, Marie Y, Alshehhi H, Carpentier C, Boisselier B, Laigle-Donadey F, Mokhtari K, Scheinin I, Wesseling P, Ylstra B, Capelle L, Hoang-Xuan K, Sanson M, Delattre JY, Reijneveld JC, and Idbaih A

Subjects
Adult, Brain Neoplasms genetics, Chromosomes, Human, Pair 1 genetics, Female, Glioblastoma genetics, Humans, Male, Middle Aged, Survival Analysis, Brain Neoplasms diagnosis, Chromosome Deletion, Chromosomes, Human, Pair 11 genetics, Chromosomes, Human, Pair 19 genetics, Glioblastoma diagnosis
Abstract

Background: Diffuse low-grade gliomas (LGGs) form a heterogeneous subgroup of gliomas in adults. Chromosome (chr) arms 1p/19q codeletion and IDH mutation have been shown to be closely associated with oligodendroglial phenotype and better prognosis. We sought to identify relevant biomarkers in non 1p/19q codeleted LGGs., Methods: We characterized a retrospective series of 126 LGGs using genomic arrays, microsatellite analysis, IDH sequencing, MGMT promoter methylation assay, and p53 expression analysis., Results: Our study confirms that 1p/19q codeletion, mutually exclusive with p53 overexpression, was associated with: (i) better prognosis, (ii) oligodendroglial phenotype, (iii) MGMT promoter methylation, and (iv) IDH mutation. Interestingly, 1p/19q codeleted tumors occur in older patients at diagnosis. Our study shows that non 1p/19q codeleted LGGs can be divided in 5 main genomic subgroups: (i) 11p loss, (ii) 19q loss (iii) 7 gain, (iv) 19 gain, and (v) unclassified. In non 1p/19q codeleted LGGs, we demonstrated that (i) 11p loss is associated with astrocytoma phenotype and has an independent negative prognostic value, and (ii) 19q loss diminished the favorable prognostic value of IDH mutation. Our findings were validated in an independent cohort of 98 LGGs., Conclusion: Novel genomic entities and biomarkers have been identified in non 1p/19q codeleted LGGs. Our findings may help to stratify non 1p/19q codeleted LGGs, facilitating future individualization of treatment. Further prospective studies are warranted to support our findings.

Published
2014
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