Comprehensive Analysis of Hypermutation in Human Cancer
Standard
Comprehensive Analysis of Hypermutation in Human Cancer. / Campbell, Brittany B; Light, Nicholas; Fabrizio, David; Zatzman, Matthew; Fuligni, Fabio; de Borja, Richard; Davidson, Scott; Edwards, Melissa; Elvin, Julia A; Hodel, Karl P; Zahurancik, Walter J; Suo, Zucai; Lipman, Tatiana; Wimmer, Katharina; Kratz, Christian P; Bowers, Daniel C; Laetsch, Theodore W; Dunn, Gavin P; Johanns, Tanner M; Grimmer, Matthew R; Smirnov, Ivan V; Larouche, Valérie; Samuel, David; Bronsema, Annika; Osborn, Michael; Stearns, Duncan; Raman, Pichai; Cole, Kristina A; Storm, Phillip B; Yalon, Michal; Opocher, Enrico; Mason, Gary; Thomas, Gregory A; Sabel, Magnus; George, Ben; Ziegler, David S; Lindhorst, Scott; Issai, Vanan Magimairajan; Constantini, Shlomi; Toledano, Helen; Elhasid, Ronit; Farah, Roula; Dvir, Rina; Dirks, Peter; Huang, Annie; Galati, Melissa A; Chung, Jiil; Ramaswamy, Vijay; Irwin, Meredith S; Aronson, Melyssa; Durno, Carol; Taylor, Michael D; Rechavi, Gideon; Maris, John M; Bouffet, Eric; Hawkins, Cynthia; Costello, Joseph F; Meyn, M Stephen; Pursell, Zachary F; Malkin, David; Tabori, Uri; Shlien, Adam.
In: CELL, Vol. 171, No. 5, 16.11.2017, p. 1042-1056.e10.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Comprehensive Analysis of Hypermutation in Human Cancer
AU - Campbell, Brittany B
AU - Light, Nicholas
AU - Fabrizio, David
AU - Zatzman, Matthew
AU - Fuligni, Fabio
AU - de Borja, Richard
AU - Davidson, Scott
AU - Edwards, Melissa
AU - Elvin, Julia A
AU - Hodel, Karl P
AU - Zahurancik, Walter J
AU - Suo, Zucai
AU - Lipman, Tatiana
AU - Wimmer, Katharina
AU - Kratz, Christian P
AU - Bowers, Daniel C
AU - Laetsch, Theodore W
AU - Dunn, Gavin P
AU - Johanns, Tanner M
AU - Grimmer, Matthew R
AU - Smirnov, Ivan V
AU - Larouche, Valérie
AU - Samuel, David
AU - Bronsema, Annika
AU - Osborn, Michael
AU - Stearns, Duncan
AU - Raman, Pichai
AU - Cole, Kristina A
AU - Storm, Phillip B
AU - Yalon, Michal
AU - Opocher, Enrico
AU - Mason, Gary
AU - Thomas, Gregory A
AU - Sabel, Magnus
AU - George, Ben
AU - Ziegler, David S
AU - Lindhorst, Scott
AU - Issai, Vanan Magimairajan
AU - Constantini, Shlomi
AU - Toledano, Helen
AU - Elhasid, Ronit
AU - Farah, Roula
AU - Dvir, Rina
AU - Dirks, Peter
AU - Huang, Annie
AU - Galati, Melissa A
AU - Chung, Jiil
AU - Ramaswamy, Vijay
AU - Irwin, Meredith S
AU - Aronson, Melyssa
AU - Durno, Carol
AU - Taylor, Michael D
AU - Rechavi, Gideon
AU - Maris, John M
AU - Bouffet, Eric
AU - Hawkins, Cynthia
AU - Costello, Joseph F
AU - Meyn, M Stephen
AU - Pursell, Zachary F
AU - Malkin, David
AU - Tabori, Uri
AU - Shlien, Adam
N1 - Copyright © 2017 Elsevier Inc. All rights reserved.
PY - 2017/11/16
Y1 - 2017/11/16
N2 - We present an extensive assessment of mutation burden through sequencing analysis of >81,000 tumors from pediatric and adult patients, including tumors with hypermutation caused by chemotherapy, carcinogens, or germline alterations. Hypermutation was detected in tumor types not previously associated with high mutation burden. Replication repair deficiency was a major contributing factor. We uncovered new driver mutations in the replication-repair-associated DNA polymerases and a distinct impact of microsatellite instability and replication repair deficiency on the scale of mutation load. Unbiased clustering, based on mutational context, revealed clinically relevant subgroups regardless of the tumors' tissue of origin, highlighting similarities in evolutionary dynamics leading to hypermutation. Mutagens, such as UV light, were implicated in unexpected cancers, including sarcomas and lung tumors. The order of mutational signatures identified previous treatment and germline replication repair deficiency, which improved management of patients and families. These data will inform tumor classification, genetic testing, and clinical trial design.
AB - We present an extensive assessment of mutation burden through sequencing analysis of >81,000 tumors from pediatric and adult patients, including tumors with hypermutation caused by chemotherapy, carcinogens, or germline alterations. Hypermutation was detected in tumor types not previously associated with high mutation burden. Replication repair deficiency was a major contributing factor. We uncovered new driver mutations in the replication-repair-associated DNA polymerases and a distinct impact of microsatellite instability and replication repair deficiency on the scale of mutation load. Unbiased clustering, based on mutational context, revealed clinically relevant subgroups regardless of the tumors' tissue of origin, highlighting similarities in evolutionary dynamics leading to hypermutation. Mutagens, such as UV light, were implicated in unexpected cancers, including sarcomas and lung tumors. The order of mutational signatures identified previous treatment and germline replication repair deficiency, which improved management of patients and families. These data will inform tumor classification, genetic testing, and clinical trial design.
KW - Journal Article
U2 - 10.1016/j.cell.2017.09.048
DO - 10.1016/j.cell.2017.09.048
M3 - SCORING: Journal article
C2 - 29056344
VL - 171
SP - 1042-1056.e10
JO - CELL
JF - CELL
SN - 0092-8674
IS - 5
ER -