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IRIS
: Many primary tumours have low levels of molecular oxygen (hypoxia), and hypoxic tumours respond poorly to therapy. Pan-cancer molecular hallmarks of tumour hypoxia remain poorly understood, with limited comprehension of its associations with specific mutational processes, non-coding driver genes and evolutionary features. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 cancers across 38 tumour types, we quantify hypoxia in 1188 tumours spanning 27 cancer types. Elevated hypoxia associates with increased mutational load across cancer types, irrespective of underlying mutational class. The proportion of mutations attributed to several mutational signatures of unknown aetiology directly associates with the level of hypoxia, suggesting underlying mutational processes for these signatures. At the gene level, driver mutations in TP53, MYC and PTEN are enriched in hypoxic tumours, and mutations in PTEN interact with hypoxia to direct tumour evolutionary trajectories. Overall, hypoxia plays a critical role in shaping the genomic and evolutionary landscapes of cancer.
Divergent mutational processes distinguish hypoxic and normoxic tumours
Bhandari, Vinayak;Li, Constance H.;Bristow, Robert G.;Boutros, Paul C.;Aaltonen, Lauri A.;Abascal, Federico;Abeshouse, Adam;Aburatani, Hiroyuki;Adams, David J.;Agrawal, Nishant;Ahn, Keun Soo;Ahn, Sung-Min;Aikata, Hiroshi;Akbani, Rehan;Akdemir, Kadir C.;Al-Ahmadie, Hikmat;Al-Sedairy, Sultan T.;Al-Shahrour, Fatima;Alawi, Malik;Albert, Monique;Aldape, Kenneth;Alexandrov, Ludmil B.;Ally, Adrian;Alsop, Kathryn;Alvarez, Eva G.;Amary, Fernanda;Amin, Samirkumar B.;Aminou, Brice;Ammerpohl, Ole;Anderson, Matthew J.;Ang, Yeng;Antonello, Davide;Anur, Pavana;Aparicio, Samuel;Appelbaum, Elizabeth L.;Arai, Yasuhito;Aretz, Axel;Arihiro, Koji;Ariizumi, Shun-ichi;Armenia, Joshua;Arnould, Laurent;Asa, Sylvia;Assenov, Yassen;Atwal, Gurnit;Aukema, Sietse;Auman, J. Todd;Aure, Miriam R. 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F.;Thompson, R. Houston;Thorne, Heather;Thorne, Leigh B.;Thorogood, Adrian;Tiao, Grace;Tijanic, Nebojsa;Timms, Lee E.;Tirabosco, Roberto;Tojo, Marta;Tommasi, Stefania;Toon, Christopher W.;Toprak, Umut H.;Torrents, David;Tortora, Giampaolo;Tost, Jörg;Totoki, Yasushi;Townend, David;Traficante, Nadia;Treilleux, Isabelle;Trotta, Jean-Rémi;Trümper, Lorenz H. P.;Tsao, Ming;Tsunoda, Tatsuhiko;Tubio, Jose M. C.;Tucker, Olga;Turkington, Richard;Turner, Daniel J.;Tutt, Andrew;Ueno, Masaki;Ueno, Naoto T.;Umbricht, Christopher;Umer, Husen M.;Underwood, Timothy J.;Urban, Lara;Urushidate, Tomoko;Ushiku, Tetsuo;Uusküla-Reimand, Liis;Valencia, Alfonso;Van Den Berg, David J.;Van Laere, Steven;Van Loo, Peter;Van Meir, Erwin G.;Van den Eynden, Gert G.;Van der Kwast, Theodorus;Vasudev, Naveen;Vazquez, Miguel;Vedururu, Ravikiran;Veluvolu, Umadevi;Vembu, Shankar;Verbeke, Lieven P. C.;Vermeulen, Peter;Verrill, Clare;Viari, Alain;Vicente, David;Vicentini, Caterina;VijayRaghavan, K.;Viksna, Juris;Vilain, Ricardo E.;Villasante, Izar;Vincent-Salomon, Anne;Visakorpi, Tapio;Voet, Douglas;Vyas, Paresh;Vázquez-García, Ignacio;Waddell, Nick M.;Waddell, Nicola;Wadelius, Claes;Wadi, Lina;Wagener, Rabea;Wala, Jeremiah A.;Wang, Jian;Wang, Jiayin;Wang, Linghua;Wang, Qi;Wang, Wenyi;Wang, Yumeng;Wang, Zhining;Waring, Paul M.;Warnatz, Hans-Jörg;Warrell, Jonathan;Warren, Anne Y.;Waszak, Sebastian M.;Wedge, David C.;Weichenhan, Dieter;Weinberger, Paul;Weinstein, John N.;Weischenfeldt, Joachim;Weisenberger, Daniel J.;Welch, Ian;Wendl, Michael C.;Werner, Johannes;Whalley, Justin P.;Wheeler, David A.;Whitaker, Hayley C.;Wigle, Dennis;Wilkerson, Matthew D.;Williams, Ashley;Wilmott, James S.;Wilson, Gavin W.;Wilson, Julie M.;Wilson, Richard K.;Winterhoff, Boris;Wintersinger, Jeffrey A.;Wiznerowicz, Maciej;Wolf, Stephan;Wong, Bernice H.;Wong, Tina;Wong, Winghing;Woo, Youngchoon;Wood, Scott;Wouters, Bradly G.;Wright, Adam J.;Wright, Derek W.;Wright, Mark H.;Wu, Chin-Lee;Wu, Dai-Ying;Wu, Guanming;Wu, Jianmin;Wu, Kui;Wu, Yang;Wu, Zhenggang;Xi, Liu;Xia, Tian;Xiang, Qian;Xiao, Xiao;Xing, Rui;Xiong, Heng;Xu, Qinying;Xu, Yanxun;Xue, Hong;Yachida, Shinichi;Yakneen, Sergei;Yamaguchi, Rui;Yamaguchi, Takafumi N.;Yamamoto, Masakazu;Yamamoto, Shogo;Yamaue, Hiroki;Yang, Fan;Yang, Huanming;Yang, Jean Y.;Yang, Liming;Yang, Lixing;Yang, Shanlin;Yang, Tsun-Po;Yang, Yang;Yao, Xiaotong;Yaspo, Marie-Laure;Yates, Lucy;Yau, Christina;Ye, Chen;Ye, Kai;Yellapantula, Venkata D.;Yoon, Christopher J.;Yoon, Sung-Soo;Yousif, Fouad;Yu, Jun;Yu, Kaixian;Yu, Willie;Yu, Yingyan;Yuan, Ke;Yuan, Yuan;Yuen, Denis;Yung, Christina K.;Zaikova, Olga;Zamora, Jorge;Zapatka, Marc;Zenklusen, Jean C.;Zenz, Thorsten;Zeps, Nikolajs;Zhang, Cheng-Zhong;Zhang, Fan;Zhang, Hailei;Zhang, Hongwei;Zhang, Hongxin;Zhang, Jiashan;Zhang, Jing;Zhang, Junjun;Zhang, Xiuqing;Zhang, Xuanping;Zhang, Yan;Zhang, Zemin;Zhao, Zhongming;Zheng, Liangtao;Zheng, Xiuqing;Zhou, Wanding;Zhou, Yong;Zhu, Bin;Zhu, Hongtu;Zhu, Jingchun;Zhu, Shida;Zou, Lihua;Zou, Xueqing;deFazio, Anna;van As, Nicholas;van Deurzen, Carolien H. M.;van de Vijver, Marc J.;van't Veer, L.;von Mering, Christian;null, null
2020-01-01
Abstract
: Many primary tumours have low levels of molecular oxygen (hypoxia), and hypoxic tumours respond poorly to therapy. Pan-cancer molecular hallmarks of tumour hypoxia remain poorly understood, with limited comprehension of its associations with specific mutational processes, non-coding driver genes and evolutionary features. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 cancers across 38 tumour types, we quantify hypoxia in 1188 tumours spanning 27 cancer types. Elevated hypoxia associates with increased mutational load across cancer types, irrespective of underlying mutational class. The proportion of mutations attributed to several mutational signatures of unknown aetiology directly associates with the level of hypoxia, suggesting underlying mutational processes for these signatures. At the gene level, driver mutations in TP53, MYC and PTEN are enriched in hypoxic tumours, and mutations in PTEN interact with hypoxia to direct tumour evolutionary trajectories. Overall, hypoxia plays a critical role in shaping the genomic and evolutionary landscapes of cancer.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11571/1497618
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simulazione ASN
Il report seguente simula gli indicatori relativi alla propria produzione scientifica in relazione alle soglie ASN 2023-2025 del proprio SC/SSD. Si ricorda che il superamento dei valori soglia (almeno 2 su 3) è requisito necessario ma non sufficiente al conseguimento dell'abilitazione. La simulazione si basa sui dati IRIS e sugli indicatori bibliometrici alla data indicata e non tiene conto di eventuali periodi di congedo obbligatorio, che in sede di domanda ASN danno diritto a incrementi percentuali dei valori. La simulazione può differire dall'esito di un’eventuale domanda ASN sia per errori di catalogazione e/o dati mancanti in IRIS, sia per la variabilità dei dati bibliometrici nel tempo. Si consideri che Anvur calcola i valori degli indicatori all'ultima data utile per la presentazione delle domande.
La presente simulazione è stata realizzata sulla base delle specifiche raccolte sul tavolo ER del Focus Group IRIS coordinato dall’Università di Modena e Reggio Emilia e delle regole riportate nel DM 589/2018 e allegata Tabella A. Cineca, l’Università di Modena e Reggio Emilia e il Focus Group IRIS non si assumono alcuna responsabilità in merito all’uso che il diretto interessato o terzi faranno della simulazione. Si specifica inoltre che la simulazione contiene calcoli effettuati con dati e algoritmi di pubblico dominio e deve quindi essere considerata come un mero ausilio al calcolo svolgibile manualmente o con strumenti equivalenti.