المؤلفون: Ally, A, Balasundaram, M, Carlsen, R, Chuah, E, Clarke, A, Dhalla, N, Holt, RA, Jones, SJM, Lee, D, Ma, Y, Marra, MA, Mayo, M, Moore, RA, Mungall, AJ, Schein, JE, Sipahimalani, P, Tam, A, Thiessen, N, Cheung, D, Wong, T, Brooks, D, Robertson, AG, Bowlby, R, Mungall, K, Sadeghi, S, Xi, L, Covington, K, Shinbrot, E, Wheeler, DA, Gibbs, RA, Donehower, LA, Wang, L, Bowen, J, Gastier-Foster, JM, Gerken, M, Helsel, C, Leraas, KM, Lichtenberg, TM, Ramirez, NC, Wise, L, Zmuda, E, Gabriel, SB, Meyerson, M, Cibulskis, C, Murray, BA, Shih, J, Beroukhim, R, Cherniack, AD, Schumacher, SE, Saksena, G, Pedamallu, CS, Chin, L, Getz, G, Noble, M, Zhang, H, Heiman, D, Cho, J, Gehlenborg, N, Voet, D, Lin, P, Frazer, S, Defreitas, T, Meier, S, Lawrence, M, Kim, J, Creighton, CJ, Muzny, D, Doddapaneni, H, Hu, J, Wang, M, Morton, D, Korchina, V, Han, Y, Dinh, H, Lewis, L, Bellair, M, Liu, X, Santibanez, J, Glenn, R, Lee, S, Hale, W, Parker, JS, Wilkerson, MD, Hayes, DN, Reynolds, SM, Shmulevich, I, Zhang, W, Liu, Y, Iype, L, Makhlouf, H, Torbenson, MS, Kakar, S, Yeh, MM, Kleiner, DE, Jain, D, Dhanasekaran, R, El-Serag, HB, Yim, SY, Weinstein, JN, Mishra, L, Zhang, J, Akbani, R, Ling, S, Ju, Z, Su, X, Hegde, AM, Mills, GB, Lu, Y, Chen, J, Lee, J-S, Sohn, BH, Shim, JJ, Tong, P, Aburatani, H, Yamamoto, S, Tatsuno, K, Li, W, Xia, Z, Stransky, N, Seiser, E, Innocenti, F, Gao, J, Kundra, R, Heins, Z, Ochoa, A, Sander, C, Ladanyi, M, Shen, R, Arora, A, Sanchez-Vega, F, Schultz, N, Kasaian, K, Radenbaugh, A, Bissig, K-D, Moore, DD, Totoki, Y, Nakamura, H, Shibata, T, Yau, C, Graim, K, Stuart, J, Haussler, D, Slagle, BL, Ojesina, AI, Katsonis, P, Koire, A, Lichtarge, O, Hsu, T-K, Ferguson, ML, Demchok, JA, Felau, I, Sheth, M, Tarnuzzer, R, Wang, Z, Yang, L, Zenklusen, JC, Hutter, CM, Sofia, HJ, Verhaak, RGW, Zheng, S, Lang, F, Chudamani, S, Liu, J, Lolla, L, Wu, Y, Naresh, R, Pihl, T, Sun, C, Wan, Y, Benz, C, Perou, AH, Thorne, LB, Boice, L, Huang, M, Rathmell, WK, Noushmehr, H, Saggioro, FP, Tirapelli, DPDC, Carlotti, CGJ, Mente, ED, Silva, ODC, Trevisan, FA, Kang, KJ, Ahn, KS, Giama, NH, Moser, CD, Giordano, TJ, Vinco, M, Welling, TH, Crain, D, Curley, E, Gardner, J, Mallery, D, Morris, S, Paulauskis, J, Penny, R, Shelton, C, Shelton, T, Kelley, RK, Park, J-W, Chandan, VS, Roberts, LR, Bathe, OF, Hagedorn, CH, Auman, JT, O'Brien, DR, Kocher, J-PA, Jones, CD, Mieczkowski, PA, Perou, CM, Skelly, T, Tan, D, Veluvolu, U, Balu, S, Bodenheimer, T, Hoyle, AP, Jefferys, SR, Meng, S, Mose, LE, Shi, Y, Simons, JV, Soloway, MG, Roach, J, Hoadley, KA, Baylin, SB, Shen, H, Hinoue, T, Bootwalla, MS, Van den Berg, DJ, Weisenberger, DJ, Lai, PH, Holbrook, A, Berrios, M, Laird, PW

المصدر: Cell , 169 (7) 1327-1341.e23. (2017)

مصطلحات موضوعية: Cell Biology, RNA-SEQ DATA, LIVER-CANCER, MUTATIONAL LANDSCAPE, THERAPEUTIC TARGETS, EXPRESSION PROFILES, SEQUENCING DATA, GENE, DNA, PREDICTION, DISCOVERY

الوصف: Liver cancer has the second highest worldwide cancer mortality rate and has limited therapeutic options. We analyzed 363 hepatocellular carcinoma (HCC) cases by whole-exome sequencing and DNA copy number analyses, and we analyzed 196 HCC cases by DNA methylation, RNA, miRNA, and proteomic expression also. DNA sequencing and mutation analysis identified significantly mutated genes, including LZTR1, EEF1A1, SF3B1, and SMARCA4. Significant alterations by mutation or downregulation by hypermethylation in genes likely to result in HCC metabolic reprogramming (ALB, APOB, and CPS1) were observed. Integrative molecular HCC subtyping incorporating unsupervised clustering of five data platforms identified three subtypes, one of which was associated with poorer prognosis in three HCC cohorts. Integrated analyses enabled development of a p53 target gene expression signature correlating with poor survival. Potential therapeutic targets for which inhibitors exist include WNT signaling, MDM4, MET, VEGFA, MCL1, IDH1, TERT, and immune checkpoint proteins CTLA-4, PD-1, and PD-L1.

وصف الملف: text

العلاقة: https://discovery.ucl.ac.uk/id/eprint/10038903/1/1-s2.0-S0092867417306396-main.pdfTest; https://discovery.ucl.ac.uk/id/eprint/10038903Test/

الإتاحة: https://discovery.ucl.ac.uk/id/eprint/10038903/1/1-s2.0-S0092867417306396-main.pdfTest
https://discovery.ucl.ac.uk/id/eprint/10038903Test/

المؤلفون: Lazar, AJ, McLellan, MD, Bailey, MH, Miller, CA, Appelbaum, EL, Cordes, MG, Fronick, CC, Fulton, LA, Fulton, RS, Mardis, ER, Schmidt, HK, Wong, W, Wilson, RK, Yellapantula, V, Radenbaugh, AJ, Hoadley, KA, Hayes, DN, Parker, JS, Wilkerson, MD, Auman, JT, Balu, S, Bodenheimer, T, Hoyle, AP, Jefferys, SR, Jones, CD, Lehmann, K-V, Meng, S, Mieczkowski, PA, Mose, LE, Perou, CM, Roach, J, Senbabaoglu, Y, Shi, Y, Simons, JV, Skelly, T, Soloway, MG, Tan, D, Veluvolu, U, Davis, IJ, Hepperla, AJ, Brohl, AS, Kasaian, K, Mungall, K, Sadeghi, S, Barthel, FP, Verhaak, R, Hu, X, Chibon, F, Cherniack, AD, Shih, J, Beroukhim, R, Meyerson, M, Cibulskis, C, Gabriel, SB, Saksena, G, Schumacher, SE, Gao, Q, Wyczalkowski, M, Bowlby, R, Robertson, AG, Ally, A, Balasundaram, M, Brooks, D, Carlsen, R, Chuah, E, Dhalla, N, Holt, RA, Jones, SJM, Lee, D, Li, I, Ma, Y, Marra, MA, Mayo, M, Moore, RA, Mungall, AJ, Schein, JE, Sipahimalani, P, Tam, A, Thiessen, N, Wong, T, Danilova, L, Cope, L, Baylin, SB, Bootwalla, MS, Lai, PH, Laird, PW, Maglinte, DT, Van Den Berg, DJ, Weisenberger, DJ, Wrangle, J, Drill, E, Shen, R, Iype, L, Reynolds, SM, Shmulevich, I, Yau, C, Armenia, J, Liu, EM, Benz, C, Pastore, A, Sanchez-Vega, F, Schultz, N, Akbani, R, Hegde, AM, Liu, W, Lu, Y, Mills, GB, Weinstein, JN, Roszik, J, Anur, P, Spellman, P, Abeshouse, A, Chen, H-W, Gao, J, Heins, Z, Kundra, R, Larsson, E, Ochoa, A, Sander, C, Socci, N, Zhang, H, Noble, MS, Heiman, DI, Kim, J, Chin, L, Getz, G, Cho, J, Defreitas, T, Frazer, S, Gehlenborg, N, Lawrence, MS, Lin, P, Meier, S, Voet, D, Byers, L, Diao, L, Gay, CM, Wang, J, Newton, Y, Cooper, LAD, Gutman, DA, Lee, S, Nalisnik, M, Bowen, J, Gastier-Foster, JM, Gerken, M, Helsel, C, Hobensack, S, Leraas, KM, Lichtenberg, TM, Ramirez, NC, Wise, L, Zmuda, E, Anderson, ML, Castro, P, Ittmann, M, Gordienko, E, Paklina, O, Setdikova, G, Raut, CP, Karlan, BY, Lester, J, Belyaev, D, Fulidou, V, Potapova, O, Voronina, O, Demetri, GD, Ramalingam, SS, Behera, M, Delman, K, Owonikoko, TK, Sica, GL, Boyd, J, Magliocco, A, Salner, A, Bennett, J, Iacocca, M, Swanson, P, Dottino, P, Kalir, T, Pereira, E, Akeredolu, T, Crain, D, Curley, E, Gardner, J, Mallery, D, Morris, S, Paulauskis, J, Penny, R, Shelton, C, Shelton, T, Thompson, E, Hoon, DB, Parfitt, J, Birrer, M, Karseladze, A, Mariamidze, A, Dao, F, Levine, DA, Olvera, N, Maki, RG, Bartlett, J, Eschbacher, J, Dubina, M, Mozgovoy, E, Fedosenko, K, Manikhas, G, Sekhon, H, Ramirez, N, Ingram, DR, Torres, KE, DiSaia, P, Godwin, AK, Godwin, EM, Kuo, H, Madan, R, Reilly, C, Adebamowo, C, Adebamowo, SN, Bocklage, T, Higgins, K, Martinez, C, Boice, L, Grilley-Olson, JE, Huang, M, Perou, AH, Thorne, LB, Rathmell, WK, Gutmann, DH, Singer, S, Chudamani, S, Liu, J, Lolla, L, Naresh, R, Pihl, T, Sun, Q, Wan, Y, Wu, Y, Felau, I, Zenklusen, JC, Demchok, JA, Ferguson, ML, Hutter, CM, Sofia, HJ, Tarnuzzer, R, Wang, Z, Yang, L, Zhang, JJ, Demicco, EG, Doyle, LA, Hornick, JL, Rubin, BP, de Rijn, MV, Baker, L, Riedel, RF, Ding, L, Ladanyi, M, Novak, JE, Van Tine, BA, Davis, LE, Grilley-Olsen, JE, Pollock, RE, Jones, KB, Martignetti, JA, Tong, P

المصدر: Cell , 171 (4) 950-965.e28. (2017)

مصطلحات موضوعية: Science & Technology, Life Sciences & Biomedicine, Biochemistry & Molecular Biology, Cell Biology, SINGLE NUCLEOTIDE POLYMORPHISMS, SMOOTH-MUSCLE DIFFERENTIATION, SOMATIC POINT MUTATIONS, COPY NUMBER ALTERATION, SEQUENCING DATA, HUMAN CANCER, GENE-EXPRESSION, DISCOVERY, CELLS, VALIDATION

الوصف: Summary Sarcomas are a broad family of mesenchymal malignancies exhibiting remarkable histologic diversity. We describe the multi-platform molecular landscape of 206 adult soft tissue sarcomas representing 6 major types. Along with novel insights into the biology of individual sarcoma types, we report three overarching findings: (1) unlike most epithelial malignancies, these sarcomas (excepting synovial sarcoma) are characterized predominantly by copy-number changes, with low mutational loads and only a few genes (TP53, ATRX, RB1) highly recurrently mutated across sarcoma types; (2) within sarcoma types, genomic and regulomic diversity of driver pathways defines molecular subtypes associated with patient outcome; and (3) the immune microenvironment, inferred from DNA methylation and mRNA profiles, associates with outcome and may inform clinical trials of immune checkpoint inhibitors. Overall, this large-scale analysis reveals previously unappreciated sarcoma-type-specific changes in copy number, methylation, RNA, and protein, providing insights into refining sarcoma therapy and relationships to other cancer types.

وصف الملف: text

العلاقة: https://discovery.ucl.ac.uk/id/eprint/10038678/1/1-s2.0-S0092867417312035-main.pdfTest; https://discovery.ucl.ac.uk/id/eprint/10038678Test/

الإتاحة: https://discovery.ucl.ac.uk/id/eprint/10038678/1/1-s2.0-S0092867417312035-main.pdfTest
https://discovery.ucl.ac.uk/id/eprint/10038678Test/

المؤلفون: Kim, J, Bowlby, R, Mungall, AJ, Robertson, AG, Odze, RD, Cherniack, AD, Shih, J, Pedamallu, CS, Cibulskis, C, Dunford, A, Meier, SR, Raphael, BJ, Wu, H-T, Wong, AM, Willis, JE, Bass, AJ, Derks, S, Garman, K, McCall, SJ, Wiznerowicz, M, Pantazi, A, Parfenov, M, Thorsson, V, Shmulevich, I, Dhankani, V, Miller, M, Sakai, R, Wang, K, Schultz, N, Shen, R, Arora, A, Weinhold, N, Sanchez-Vega, F, Kelsen, DP, Zhang, J, Felau, I, Demchok, J, Rabkin, CS, Camargo, MC, Zenklusen, JC, Bowen, J, Leraas, K, Lichtenberg, TM, Curtis, C, Seoane, JA, Ojesina, AI, Beer, DG, Gulley, ML, Pennathur, A, Luketich, JD, Zhou, Z, Weisenberger, DJ, Akbani, R, Lee, J-S, Liu, W, Mills, GB, Zhang, W, Reid, BJ, Hinoue, T, Laird, PW, Shen, H, Piazuelo, MB, Schneider, BG, McLellan, M, Taylor-Weiner, A, Lawrence, M, Cibulskis, K, Stewart, C, Getz, G, Lander, E, Gabriel, SB, Ding, L, McLellan, MD, Miller, CA, Appelbaum, EL, Cordes, MG, Fronick, CC, Fulton, LA, Mardis, ER, Wilson, RK, Schmidt, HK, Fulton, RS, Ally, A, Balasundaram, M, Carlsen, R, Chuah, E, Dhalla, N, Holt, RA, Jones, SJM, Kasaian, K, Brooks, D, Li, HI, Ma, Y, Marra, MA, Mayo, M, Moore, RA, Mungall, KL, Schein, JE, Sipahimalani, P, Tam, A, Thiessen, N, Wong, T, Beroukhim, R, Bullman, S, Murray, BA, Saksena, G, Schumacher, SE, Gabriel, S, Meyerson, M, Hadjipanayis, A, Kucherlapati, R, Ren, X, Park, PJ, Lee, S, Kucherlapati, M, Yang, L, Baylin, SB, Hoadley, KA, Bootwalla, MS, Lai, PH, Van den Berg, DJ, Berrios, M, Holbrook, A, Hwang, J-E, Jang, H-J, Weinstein, JN, Lu, Y, Sohn, BH, Mills, G, Seth, S, Protopopov, A, Bristow, CA, Mahadeshwar, HS, Tang, J, Song, X, Cho, J, Defrietas, T, Frazer, S, Gehlenborg, N, Heiman, DI, Lawrence, MS, Lin, P, Noble, MS, Doug, V, Zhang, H, Polak, P, Chin, L, Bernard, B, Iype, L, Reynolds, SM, Abeshouse, A, Armenia, J, Kundra, R, Ladanyi, M, Kjong-Van, L, Gao, J, Sander, C, Chakravarty, D, Radenbaugh, A, Hegde, A, Penny, R, Crain, D, Gardner, J, Curley, E, Mallery, D, Morris, S, Paulauskis, J, Shelton, T, Shelton, C, Frick, J, Gastier-Foster, JM, Gerken, M, Leraas, KM, Ramirez, NC, Wise, L, Zmuda, E, Tarvin, K, Saller, C, Park, YS, Button, M, Carvalho, AL, Reis, RM, Matsushita, MM, Lucchesi, F, de Oliveira, AT, Le, X, Paklina, O, Setdikova, G, Lee, J-H, Bennett, J, Iacocca, M, Huelsenbeck-Dill, L, Potapova, CO, Voronina, O, Liu, O, Fulidou, V, Cates, C, Sharp, A, Behera, M, Force, S, Khuri, F, Owonikoko, T, Pickens, A, Ramalingam, S, Sica, G, Dinjens, W, van Nistelrooij, A, Wijnhoven, B, Sandusky, G, Stepa, S, Juhl, IH, Zornig, C, Kwon, SY, Kelsen, D, Kim, GHK, Bartlett, J, Parfitt, J, Chetty, R, Darling, G, Knox, J, Wong, R, El-Zimaity, H, Liu, G, Boussioutas, A, Park, DY, Kemp, R, Carlotti, CG, da Cunha Tirapelli, DP, Saggioro, FP, Sankarankutty, AK, Noushmehr, H, dos Santos, JS, Trevisan, FA, Eschbacher, J, Dubina, M, Mozgovoy, E, Carey, F, Chalmers, S, Forgie, I, Godwin, A, Reilly, C, Madan, R, Naima, Z, Ferrer-Torres, D, Rathmell, WK, Dhir, R, Luketich, J, Ajani, JA, Janjigian, Y, Tang, L, Cheong, J-H, Chudamani, S, Liu, J, Lolla, L, Naresh, R, Pihl, T, Sun, Q, Wan, Y, Wu, Y, Demchok, JA, Ferguson, ML, Shaw, KRM, sheth, M, Tarnuzzer, R, Wang, Z, Hutter, CM, Sofia, HJ

الوصف: Oesophageal cancers are prominent worldwide; however, there are few targeted therapies and survival rates for these cancers remain dismal. Here we performed a comprehensive molecular analysis of 164 carcinomas of the oesophagus derived from Western and Eastern populations. Beyond known histopathological and epidemiologic distinctions, molecular features differentiated oesophageal squamous cell carcinomas from oesophageal adenocarcinomas. Oesophageal squamous cell carcinomas resembled squamous carcinomas of other organs more than they did oesophageal adenocarcinomas. Our analyses identified three molecular subclasses of oesophageal squamous cell carcinomas, but none showed evidence for an aetiological role of human papillomavirus. Squamous cell carcinomas showed frequent genomic amplifications of CCND1 and SOX2 and/or TP63, whereas ERBB2, VEGFA and GATA4 and GATA6 were more commonly amplified in adenocarcinomas. Oesophageal adenocarcinomas strongly resembled the chromosomally unstable variant of gastric adenocarcinoma, suggesting that these cancers could be considered a single disease entity. However, some molecular features, including DNA hypermethylation, occurred disproportionally in oesophageal adenocarcinomas. These data provide a framework to facilitate more rational categorization of these tumours and a foundation for new therapies.

العلاقة: pii: nature20805; Kim, J., Bowlby, R., Mungall, A. J., Robertson, A. G., Odze, R. D., Cherniack, A. D., Shih, J., Pedamallu, C. S., Cibulskis, C., Dunford, A., Meier, S. R., Kim, J., Raphael, B. J., Wu, H. -T., Wong, A. M., Willis, J. E., Bass, A. J., Derks, S., Garman, K. ,. Zhang, J. (2017). Integrated genomic characterization of oesophageal carcinoma. NATURE, 541 (7636), pp.169-+. https://doi.org/10.1038/nature20805Test.; http://hdl.handle.net/11343/258356Test

الإتاحة: https://doi.org/10.1038/nature20805Test
http://hdl.handle.net/11343/258356Test

المؤلفون: Bass, AJ, Thorsson, V, Shmulevich, I, Reynolds, SM, Miller, M, Bernard, B, Hinoue, T, Laird, PW, Curtis, C, Shen, H, Weisenberger, DJ, Schultz, N, Shen, R, Weinhold, N, Keiser, DP, Bowlby, R, Sipahimalani, P, Cherniack, AD, Getz, G, Liu, Y, Noble, MS, Pedamallu, C, Sougnez, C, Taylor-Weiner, A, Akbani, R, Lee, J-S, Liu, W, Mills, GB, Yang, D, Zhang, W, Pantazi, A, Parfenov, M, Gulley, M, Piazuelo, MB, Schneider, BG, Kim, J, Boussioutas, A, Sheth, M, Demchok, JA, Rabkin, CS, Willis, JE, Ng, S, Garman, K, Beer, DG, Pennathur, A, Raphael, BJ, Wu, H-T, Odze, R, Kim, HK, Bowen, J, Leraas, KM, Lichtenberg, TM, Weaver, L, McLellan, M, Wiznerowicz, M, Sakai, R, Lawrence, MS, Cibulskis, K, Lichtenstein, L, Fisher, S, Gabriel, SB, Lander, ES, Ding, L, Niu, B, Ally, A, Balasundaram, M, Birol, I, Brooks, D, Butterfield, YSN, Carlsen, R, Chu, A, Chu, J, Chuah, E, Chun, H-JE, Clarke, A, Dhalla, N, Guin, R, Holt, RA, Jones, SJM, Kasaian, K, Lee, D, Li, HA, Lim, E, Ma, Y, Marra, MA, Mayo, M, Moore, RA, Mungall, AJ, Mungall, KL, Nip, KM, Robertson, AG, Schein, JE, Tam, A, Thiessen, N, Beroukhim, R, Carter, SL, Cho, J, DiCara, D, Frazer, S, Gehlenborg, N, Heiman, DI, Jung, J, Lin, P, Meyerson, M, Ojesina, AI, Pedamallu, CS, Saksena, G, Schumacher, SE, Stojanov, P, Tabak, B, Voet, D, Rosenberg, M, Zack, TI, Zhang, H, Zou, L, Protopopov, A, Santoso, N, Lee, S, Zhang, J, Mahadeshwar, HS, Tang, J, Ren, X, Seth, S, Yang, L, Xu, AW, Song, X, Xi, R, Bristow, CA, Hadjipanayis, A, Seidman, J, Chin, L, Park, PJ, Kucherlapati, R, Ling, S, Rao, A, Weinstein, JN, Kim, S-B, Lu, Y, Mills, G, Bootwalla, MS, Lai, PH, Triche, T, Van Den Berg, DJ, Baylin, SB, Herman, JG, Murray, BA, Askoy, BA, Ciriello, G, Dresdner, G, Gao, J, Gross, B, Jacobsen, A, Lee, W, Ramirez, R, Sander, C, Senbabaoglu, Y, Sinha, R, Sumer, SO, Sun, Y, Iype, L, Kramer, RW, Kreisberg, R, Rovira, H, Tasman, N, Haussler, D, Stuart, JM, Verhaak, RGW, Leiserson, MDM, Taylor, BS, Black, AD, Carney, JA, Gastier-Foster, JM, Helsel, C, McAllister, C, Ramirez, NC, Tabler, TR, Wise, L, Zmuda, E, Penny, R, Crain, D, Gardner, J, Lau, K, Curely, E, Mallery, D, Morris, S, Paulauskis, J, Shelton, T, Shelton, C, Sherman, M, Benz, C, Lee, J-H, Fedosenko, K, Manikhas, G, Voronina, O, Belyaev, D, Dolzhansky, O, Rathmell, WK, Brzezinski, J, Ibbs, M, Korski, K, Kycler, W, Lazniak, R, Leporowska, E, Mackiewicz, A, Murawa, D, Murawa, P, Spychala, A, Suchorska, WM, Tatka, H, Teresiak, M, Abdel-Misih, R, Bennett, J, Brown, J, Iacocca, M, Rabeno, B, Kwon, S-Y, Kemkes, A, Curley, E, Alexopoulou, I, Engel, J, Bartlett, J, Albert, M, Park, D-Y, Dhir, R, Luketich, J, Landreneau, R, Janjigian, YY, Kelsen, DP, Cho, E, Ladanyi, M, Tang, L, McCall, SJ, Park, YS, Cheong, J-H, Ajani, J, Camargo, MC, Alonso, S, Ayala, B, Jensen, MA, Pihl, T, Raman, R, Walton, J, Wan, Y, Eley, G, Shaw, KRM, Tarnuzzer, R, Wang, Z, Zenklusen, JC, Davidsen, T, Hutter, CM, Sofia, HJ, Burton, R, Chudamani, S, Liu, J

الوصف: Gastric cancer is a leading cause of cancer deaths, but analysis of its molecular and clinical characteristics has been complicated by histological and aetiological heterogeneity. Here we describe a comprehensive molecular evaluation of 295 primary gastric adenocarcinomas as part of The Cancer Genome Atlas (TCGA) project. We propose a molecular classification dividing gastric cancer into four subtypes: tumours positive for Epstein-Barr virus, which display recurrent PIK3CA mutations, extreme DNA hypermethylation, and amplification of JAK2, CD274 (also known as PD-L1) and PDCD1LG2 (also known as PD-L2); microsatellite unstable tumours, which show elevated mutation rates, including mutations of genes encoding targetable oncogenic signalling proteins; genomically stable tumours, which are enriched for the diffuse histological variant and mutations of RHOA or fusions involving RHO-family GTPase-activating proteins; and tumours with chromosomal instability, which show marked aneuploidy and focal amplification of receptor tyrosine kinases. Identification of these subtypes provides a roadmap for patient stratification and trials of targeted therapies.

العلاقة: pii: nature13480; Bass, A. J., Thorsson, V., Shmulevich, I., Reynolds, S. M., Miller, M., Bernard, B., Hinoue, T., Laird, P. W., Curtis, C., Shen, H., Weisenberger, D. J., Schultz, N., Shen, R., Weinhold, N., Keiser, D. P., Bowlby, R., Sipahimalani, P., Cherniack, A. D., Getz, G. ,. Liu, J. (2014). Comprehensive molecular characterization of gastric adenocarcinoma. NATURE, 513 (7517), pp.202-209. https://doi.org/10.1038/nature13480Test.; http://hdl.handle.net/11343/263301Test

الإتاحة: https://doi.org/10.1038/nature13480Test
http://hdl.handle.net/11343/263301Test

المؤلفون: Fishbein, L, Leshchiner, I, Walter, V, Danilova, L, Robertson, AG, Johnson, AR, Lichtenberg, TM, Murray, BA, Ghayee, HK, Else, T, Ling, SY, Jefferys, SR, de Cubas, AA, Wenz, B, Korpershoek, Esther, Amelio, AL, Makowski, L, Rathmell, WK, Gimenez-Roqueplo, AP, Giordano, TJ, Asa, SL, Tischler, AS, Pacak, K, Nathanson, KL, Wilkerson, MD

المصدر: Fishbein , L , Leshchiner , I , Walter , V , Danilova , L , Robertson , AG , Johnson , AR , Lichtenberg , TM , Murray , BA , Ghayee , HK , Else , T , Ling , SY , Jefferys , SR , de Cubas , AA , Wenz , B , Korpershoek , E , Amelio , AL , Makowski , L , Rathmell , WK , Gimenez-Roqueplo , AP , Giordano , TJ , Asa , SL , Tischler , AS , Pacak , K , Nathanson , KL & Wilkerson , ....

الإتاحة: https://doi.org/10.1016/j.ccell.2017.01.001Test
https://pure.eur.nl/en/publications/41d2d481-f603-4b60-855e-a88bcc0170b2Test
http://hdl.handle.net/1765/95832Test

المؤلفون: Ciriello, G., Gatza, M.L., Beck, A.H., Wilkerson, M.D., Rhie, S.K., Pastore, A., Zhang, H., McLellan, M., Yau, C., Kandoth, C., Bowlby, R., Shen, H., Hayat, S., Fieldhouse, R., Lester, S.C., Tse, G.M., Factor, R.E., Collins, L.C., Allison, K.H., Chen, Y.Y., Jensen, K., Johnson, N.B., Oesterreich, S., Mills, G.B., Cherniack, A.D., Robertson, G., Benz, C., Sander, C., Laird, P.W., Hoadley, K.A., King, T.A., TCGA Research, Network, Perou, C.M.

المساهمون: TCGA Research, Network, Akbani, R., Auman, JT., Balasundaram, M., Balu, S., Barr, T., Beck, A., Benz, C., Benz, S., Berrios, M., Beroukhim, R., Bodenheimer, T., Boice, L., Bootwalla, MS., Bowen, J., Bowlby, R., Brooks, D., Cherniack, AD., Chin, L., Cho, J., Chudamani, S., Ciriello, G., Davidsen, T., Demchok, JA., Dennison, JB., Ding, L., Felau, I., Ferguson, ML., Frazer, S., Gabriel, SB., Gao, J., Gastier-Foster, JM., Gatza, ML., Gehlenborg, N., Gerken, M., Getz, G., Gibson, WJ., Hayes, DN., Heiman, DI., Hoadley, KA., Holbrook, A., Holt, RA., Hoyle, AP., Hu, H., Huang, M., Hutter, CM., Hwang, ES., Jefferys, SR., Jones, SJ., Ju, Z., Kim, J., Lai, PH., Laird, PW., Lawrence, MS., Leraas, KM., Lichtenberg, TM., Lin, P., Ling, S., Liu, J., Liu, W., Lolla, L., Lu, Y., Ma, Y., Maglinte, DT., Mardis, E., Marks, J., Marra, MA., McAllister, C., McLellan, M., Meng, S., Meyerson, M., Mills, GB., Moore, RA., Mose, LE., Mungall, AJ., Murray, BA., Naresh, R., Noble, MS., Oesterreich, S., Olopade, O., Parker, JS., Perou, CM., Pihl, T., Saksena, G., Schumacher, SE., Shaw, KR., Ramirez, NC., Rathmell, WK., Rhie, SK., Roach, J., Robertson, AG., Sander, C., Schein, JE., Schultz, N., Shen, H., Sheth, M., Shi, Y., Shih, J., Shelley, CS.

المصدر: Cell, vol. 163, no. 2, pp. 506-519

الوصف: Invasive lobular carcinoma (ILC) is the second most prevalent histologic subtype of invasive breast cancer. Here, we comprehensively profiled 817 breast tumors, including 127 ILC, 490 ductal (IDC), and 88 mixed IDC/ILC. Besides E-cadherin loss, the best known ILC genetic hallmark, we identified mutations targeting PTEN, TBX3, and FOXA1 as ILC enriched features. PTEN loss associated with increased AKT phosphorylation, which was highest in ILC among all breast cancer subtypes. Spatially clustered FOXA1 mutations correlated with increased FOXA1 expression and activity. Conversely, GATA3 mutations and high expression characterized luminal A IDC, suggesting differential modulation of ER activity in ILC and IDC. Proliferation and immune-related signatures determined three ILC transcriptional subtypes associated with survival differences. Mixed IDC/ILC cases were molecularly classified as ILC-like and IDC-like revealing no true hybrid features. This multidimensional molecular atlas sheds new light on the genetic bases of ILC and provides potential clinical options.

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/26451490; info:eu-repo/semantics/altIdentifier/eissn/1097-4172; https://serval.unil.ch/notice/serval:BIB_E5BACAE80B12Test; urn:issn:0092-8674

الإتاحة: https://doi.org/10.1016/j.cell.2015.09.033Test
https://serval.unil.ch/notice/serval:BIB_E5BACAE80B12Test