Hypermutation takes the driver's seat

被引：15

作者：

Schlesner, Matthias ^{[1
]}

Eils, Roland ^{[1
,2
,3
,4
]}

机构：

[1] German Canc Res Ctr, Div Theoret Bioinformat, D-69120 Heidelberg, Germany

[2] Heidelberg Univ, IPMB, Dept Bioinformat & Funct Genom, D-69120 Heidelberg, Germany

[3] Heidelberg Univ, BioQuant, D-69120 Heidelberg, Germany

[4] German Canc Res Ctr, HIPO, Heidelberg Ctr Personalised Oncol, D-69120 Heidelberg, Germany

来源：

GENOME MEDICINE | 2015年 / 7卷

关键词：

Chronic Lymphocytic Leukemia; Mutational Load; PolE Mutation; Repair Deficiency; Exonic Mutation;

D O I：

10.1186/s13073-015-0159-x

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Most pediatric tumors have only very few somatic mutations. However, a recent study revealed that a subset of tumors from children with congenital biallelic deficiency of DNA mismatch repair exhibits a mutational load surpassing almost all other cancers. In these ultra-hypermutated tumors, somatic mutations in the proofreading DNA polymerases complement the congenital mismatch repair deficiency to completely abolish replication repair, thereby driving tumor development. These findings open several possibilities for exploiting ultra-hypermutation for cancer therapy.

引用

页数：3

共 8 条

[1]

Aksoy BA, PREDICTION INDIVIDUA

[2] Signatures of mutational processes in human cancer [J].

Alexandrov, Ludmil B. ;

Nik-Zainal, Serena ;

Wedge, David C. ;

Aparicio, Samuel A. J. R. ;

Behjati, Sam ;

Biankin, Andrew V. ;

Bignell, Graham R. ;

Bolli, Niccolo ;

Borg, Ake ;

Borresen-Dale, Anne-Lise ;

Boyault, Sandrine ;

Burkhardt, Birgit ;

Butler, Adam P. ;

Caldas, Carlos ;

Davies, Helen R. ;

Desmedt, Christine ;

Eils, Roland ;

Eyfjord, Jorunn Erla ;

Foekens, John A. ;

Greaves, Mel ;

Hosoda, Fumie ;

Hutter, Barbara ;

Ilicic, Tomislav ;

Imbeaud, Sandrine ;

Imielinsk, Marcin ;

Jaeger, Natalie ;

Jones, David T. W. ;

Jones, David ;

Knappskog, Stian ;

Kool, Marcel ;

Lakhani, Sunil R. ;

Lopez-Otin, Carlos ;

Martin, Sancha ;

Munshi, Nikhil C. ;

Nakamura, Hiromi ;

Northcott, Paul A. ;

Pajic, Marina ;

Papaemmanuil, Elli ;

Paradiso, Angelo ;

Pearson, John V. ;

Puente, Xose S. ;

Raine, Keiran ;

Ramakrishna, Manasa ;

Richardson, Andrea L. ;

Richter, Julia ;

Rosenstiel, Philip ;

Schlesner, Matthias ;

Schumacher, Ton N. ;

Span, Paul N. ;

Teague, Jon W. .

NATURE, 2013, 500 (7463) :415-+

[3] The landscape of somatic mutations in infant MLL-rearranged acute lymphoblastic leukemias [J].

Andersson, Anna K. ;

Ma, Jing ;

Wang, Jianmin ;

Chen, Xiang ;

Gedman, Amanda Larson ;

Dang, Jinjun ;

Nakitandwe, Joy ;

Holmfeldt, Linda ;

Parker, Matthew ;

Easton, John ;

Huether, Robert ;

Kriwacki, Richard ;

Rusch, Michael ;

Wu, Gang ;

Li, Yongjin ;

Mulder, Heather ;

Raimondi, Susana ;

Pounds, Stanley ;

Kang, Guolian ;

Shi, Lei ;

Becksfort, Jared ;

Gupta, Pankaj ;

Payne-Turner, Debbie ;

Vadodaria, Bhavin ;

Boggs, Kristy ;

Yergeau, Donald ;

Manne, Jayanthi ;

Song, Guangchun ;

Edmonson, Michael ;

Nagahawatte, Panduka ;

Wei, Lei ;

Cheng, Cheng ;

Pei, Deqing ;

Sutton, Rosemary ;

Venn, Nicola C. ;

Chetcuti, Albert ;

Rush, Amanda ;

Catchpoole, Daniel ;

Heldrup, Jesper ;

Fioretos, Thoas ;

Lu, Charles ;

Ding, Li ;

Pui, Ching-Hon ;

Shurtleff, Sheila ;

Mullighan, Charles G. ;

Mardis, Elaine R. ;

Wilson, Richard K. ;

Gruber, Tanja A. ;

Zhang, Jinghui ;

Downing, James R. .

NATURE GENETICS, 2015, 47 (04) :330-U192

[4] Classification of current anticancer immunotherapies [J].

Galluzzi, Lorenzo ;

Vacchelli, Erika ;

Bravo-San Pedro, Jose-Manuel ;

Buque, Aitziber ;

Senovilla, Laura ;

Baracco, Elisa Elena ;

Bloy, Norma ;

Castoldi, Francesca ;

Abastado, Jean-Pierre ;

Agostinis, Patrizia ;

Apte, Ron N. ;

Aranda, Fernando ;

Ayyoub, Maha ;

Beckhove, Philipp ;

Blay, Jean-Yves ;

Bracci, Laura ;

Caignard, Anne ;

Castelli, Chiara ;

Cavallo, Federica ;

Celis, Estaban ;

Cerundolo, Vincenzo ;

Clayton, Aled ;

Colombo, Mario P. ;

Coussens, Lisa ;

Dhodapkar, Madhav V. ;

Eggermont, Alexander M. ;

Fearon, Douglas T. ;

Fridman, Wolf H. ;

Fucikova, Jitka ;

Gabrilovich, Dmitry I. ;

Galon, Jerome ;

Garg, Abhishek ;

Ghiringhelli, Francois ;

Giaccone, Giuseppe ;

Gilboa, Eli ;

Gnjatic, Sacha ;

Hoos, Axel ;

Hosmalin, Anne ;

Jaeger, Dirk ;

Kalinski, Pawel ;

Kaerre, Klas ;

Kepp, Oliver ;

Kiessling, Rolf ;

Kirkwood, John M. ;

Klein, Eva ;

Knuth, Alexander ;

Lewis, Claire E. ;

Liblau, Roland ;

Lotze, Michael T. ;

Lugli, Enrico .

ONCOTARGET, 2014, 5 (24) :12472-12508

[5] Hypermutation of the Inactive X Chromosome Is a Frequent Event in Cancer [J].

Jaeger, Natalie ;

Schlesner, Matthias ;

Jones, David T. W. ;

Raffel, Simon ;

Mallm, Jan-Philipp ;

Junge, Kristin M. ;

Weichenhan, Dieter ;

Bauer, Tobias ;

Ishaque, Naveed ;

Kool, Marcel ;

Northcott, Paul A. ;

Korshunov, Andrey ;

Drews, Ruben M. ;

Koster, Jan ;

Versteeg, Rogier ;

Richter, Julia ;

Hummel, Michael ;

Mack, Stephen C. ;

Taylor, Michael D. ;

Witt, Hendrik ;

Swartman, Benedict ;

Schulte-Bockholt, Dietrich ;

Sultan, Marc ;

Yaspo, Marie-Laure ;

Lehrach, Hans ;

Hutter, Barbara ;

Brors, Benedikt ;

Wolf, Stephan ;

Plass, Christoph ;

Siebert, Reiner ;

Trumpp, Andreas ;

Rippe, Karsten ;

Lehmann, Irina ;

Lichter, Peter ;

Pfister, Stefan M. ;

Eils, Roland .

CELL, 2013, 155 (03) :567-581

[6] Mutational heterogeneity in cancer and the search for new cancer-associated genes [J].

Lawrence, Michael S. ;

Stojanov, Petar ;

Polak, Paz ;

Kryukov, Gregory V. ;

Cibulskis, Kristian ;

Sivachenko, Andrey ;

Carter, Scott L. ;

Stewart, Chip ;

Mermel, Craig H. ;

Roberts, Steven A. ;

Kiezun, Adam ;

Hammerman, Peter S. ;

McKenna, Aaron ;

Drier, Yotam ;

Zou, Lihua ;

Ramos, Alex H. ;

Pugh, Trevor J. ;

Stransky, Nicolas ;

Helman, Elena ;

Kim, Jaegil ;

Sougnez, Carrie ;

Ambrogio, Lauren ;

Nickerson, Elizabeth ;

Shefler, Erica ;

Cortes, Maria L. ;

Auclair, Daniel ;

Saksena, Gordon ;

Voet, Douglas ;

Noble, Michael ;

DiCara, Daniel ;

Lin, Pei ;

Lichtenstein, Lee ;

Heiman, David I. ;

Fennell, Timothy ;

Imielinski, Marcin ;

Hernandez, Bryan ;

Hodis, Eran ;

Baca, Sylvan ;

Dulak, Austin M. ;

Lohr, Jens ;

Landau, Dan-Avi ;

Wu, Catherine J. ;

Melendez-Zajgla, Jorge ;

Hidalgo-Miranda, Alfredo ;

Koren, Amnon ;

McCarroll, Steven A. ;

Mora, Jaume ;

Lee, Ryan S. ;

Crompton, Brian ;

Onofrio, Robert .

NATURE, 2013, 499 (7457) :214-218

[7] Combined hereditary and somatic mutations of replication error repair genes result in rapid onset of ultra-hypermutated cancers [J].

Shlien, Adam ;

Campbell, Brittany B. ;

de Borja, Richard ;

Alexandrov, Ludmil B. ;

Merico, Daniele ;

Wedge, David ;

Van Loo, Peter ;

Tarpey, Patrick S. ;

Coupland, Paul ;

Behjati, Sam ;

Pollett, Aaron ;

Lipman, Tatiana ;

Heidari, Abolfazl ;

Deshmukh, Shriya ;

Avitzur, Na'ama ;

Meier, Bettina ;

Gerstung, Moritz ;

Hong, Ye ;

Merino, Diana M. ;

Ramakrishna, Manasa ;

Remke, Marc ;

Arnold, Roland ;

Panigrahi, Gagan B. ;

Thakkar, Neha P. ;

Hodel, Karl P. ;

Henninger, Erin E. ;

Goeksenin, A. Yasemin ;

Bakry, Doua ;

Charames, George S. ;

Druker, Harriet ;

Lerner-Ellis, Jordan ;

Mistry, Matthew ;

Dvir, Rina ;

Grant, Ronald ;

Elhasid, Ronit ;

Farah, Roula ;

Taylor, Glenn P. ;

Nathan, Paul C. ;

Alexander, Sarah ;

Ben-Shachar, Shay ;

Ling, Simon C. ;

Gallinger, Steven ;

Constantini, Shlomi ;

Dirks, Peter ;

Huang, Annie ;

Scherer, Stephen W. ;

Grundy, Richard G. ;

Durno, Carol ;

Aronson, Melyssa ;

Gartner, Anton .

NATURE GENETICS, 2015, 47 (03) :257-+

[8] Differential DNA mismatch repair underlies mutation rate variation across the human genome [J].

Supek, Fran ;

Lehner, Ben .

NATURE, 2015, 521 (7550) :81-U173

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