Clonal dynamics towards the development of venetoclax resistance in chronic lymphocytic leukemia

被引：174

作者：

Herling, Carmen D. ^{[1
]}

Abedpour, Nima ^{[2
,3
]}

Weiss, Jonathan ^{[1
]}

Schmitt, Anna ^{[1
,3
,4
]}

Jachimowicz, Ron Daniel ^{[1
,3
,4
]}

Merkel, Olaf ^{[1
,4
]}

Cartolano, Maria ^{[2
,3
]}

Oberbeck, Sebastian ^{[1
,3
,4
,5
]}

Mayer, Petra ^{[1
,3
,4
,5
]}

Berg, Valeska ^{[1
,4
]}

Thomalla, Daniel ^{[1
,4
]}

Kutsch, Nadine ^{[1
]}

Stiefelhagen, Marius ^{[1
]}

Cramer, Paula ^{[1
]}

Wendtner, Clemens-Martin ^{[6
]}

Persigehl, Thorsten ^{[7
]}

Saleh, Andreas ^{[8
]}

Altmueller, Janine ^{[3
,9
]}

Nuernberg, Peter ^{[3
,4
,9
]}

Pallasch, Christian ^{[1
,3
,4
]}

Achter, Viktor ^{[10
]}

Lang, Ulrich ^{[10
,11
]}

Eichhorst, Barbara ^{[1
]}

Castiglione, Roberta ^{[12
]}

Schaefer, Stephan C. ^{[12
]}

Buettner, Reinhard ^{[12
]}

Kreuzer, Karl-Anton ^{[1
]}

Reinhardt, Hans Christian ^{[1
,3
,4
]}

Hallek, Michael ^{[1
,3
,4
]}

Frenzel, Lukas P. ^{[1
,4
]}

Peifer, Martin ^{[2
,3
]}

机构：

[1] Univ Cologne, Ctr Integrated Oncol Cologne Bonn, Dept Internal Med 1, D-50937 Cologne, Germany

[2] Univ Cologne, Ctr Integrated Oncol Cologne Bonn, Dept Translat Genom, Med Fac, D-50931 Cologne, Germany

[3] Univ Cologne, CMMC, D-50931 Cologne, Germany

[4] Univ Cologne, Cologne Excellence Cluster Cellular Stress Respon, D-50931 Cologne, Germany

[5] Univ Cologne, Lab Lymphocyte Signaling & Oncoproteom, D-50931 Cologne, Germany

[6] Klinikum Schwabing, Dept Hematol Oncol Immunol Palliat Care Infect Di, D-80804 Munich, Germany

[7] Cologne Univ Hosp, Dept Radiol, D-50937 Cologne, Germany

[8] Stadtisches Klinikum Munchen Schwabing, Dept Diagnost & Intervent Radiol & Pediat Radiol, D-80804 Munich, Germany

[9] Univ Cologne, CCG, D-50931 Cologne, Germany

[10] Univ Cologne, Comp Ctr, D-50931 Cologne, Germany

[11] Univ Cologne, Dept Informat, D-50931 Cologne, Germany

[12] Univ Cologne, Dept Pathol, D-50937 Cologne, Germany

来源：

NATURE COMMUNICATIONS | 2018年 / 9卷

关键词：

CELL LUNG-CANCER; DNA METHYLATION DATA; RECURRENT MUTATIONS; RICHTER SYNDROME; EVOLUTION; TRANSFORMATION; PROGRESSION; SURVIVAL; PD-L1; CD274;

D O I：

10.1038/s41467-018-03170-7

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Deciphering the evolution of cancer cells under therapeutic pressure is a crucial step to understand the mechanisms that lead to treatment resistance. To this end, we analyzed whole-exome sequencing data of eight chronic lymphocytic leukemia (CLL) patients that developed resistance upon BCL2-inhibition by venetoclax. Here, we report recurrent mutations in BTG1 (2 patients) and homozygous deletions affecting CDKN2A/B (3 patients) that developed during treatment, as well as a mutation in BRAF and a high-level focal amplification of CD274 (PD-L1) that might pinpoint molecular aberrations offering structures for further therapeutic interventions.

引用

页数：8

共 36 条

[1]

[Anonymous], 2005, PHYLIP (phylogeny inference package) version 3.6

[2]

Assenov Y, 2014, NAT METHODS, V11, P1138, DOI [10.1038/NMETH.3115, 10.1038/nmeth.3115]

[3]

BINET JL, 1977, CANCER-AM CANCER SOC, V40, P855, DOI 10.1002/1097-0142(197708)40:2<855::AID-CNCR2820400239>3.0.CO

[4]

2-1

[5]

Activity of trametinib in K601E and L597Q BRAF mutation-positive metastatic melanoma [J].

Bowyer, Samantha E. ;

Rao, Aparna D. ;

Lyle, Megan ;

Sandhu, Shahneen ;

Long, Georgina V. ;

McArthur, Grant A. ;

Raleigh, Jeanette M. ;

Hicks, Rodney J. ;

Millward, Michael .

MELANOMA RESEARCH, 2014, 24 (05) :504-508

[6]

Safety and Activity of Anti-PD-L1 Antibody in Patients with Advanced Cancer [J].

Brahmer, Julie R. ;

Tykodi, Scott S. ;

Chow, Laura Q. M. ;

Hwu, Wen-Jen ;

Topalian, Suzanne L. ;

Hwu, Patrick ;

Drake, Charles G. ;

Camacho, Luis H. ;

Kauh, John ;

Odunsi, Kunle ;

Pitot, Henry C. ;

Hamid, Omid ;

Bhatia, Shailender ;

Martins, Renato ;

Eaton, Keith ;

Chen, Shuming ;

Salay, Theresa M. ;

Alaparthy, Suresh ;

Grosso, Joseph F. ;

Korman, Alan J. ;

Parker, Susan M. ;

Agrawal, Shruti ;

Goldberg, Stacie M. ;

Pardoll, Drew M. ;

Gupta, Ashok ;

Wigginton, Jon M. .

NEW ENGLAND JOURNAL OF MEDICINE, 2012, 366 (26) :2455-2465

[7]

Pan-Cancer Analysis of Copy Number Changes in Programmed Death-Ligand 1 (PD-L1, CD274) - Associations with Gene Expression, Mutational Load, and Survival [J].

Budczies, Jan ;

Bockmayr, Michael ;

Denkert, Carsten ;

Klauschen, Frederick ;

Groeschel, Stefan ;

Darb-Esfahani, Silvia ;

Pfarr, Nicole ;

Leichsenring, Jonas ;

Onozato, Maristela L. ;

Lennerz, Jochen K. ;

Dietel, Manfred ;

Froehling, Stefan ;

Schirmacher, Peter ;

Iafrate, A. John ;

Weichert, Wilko ;

Stenzinger, Albrecht .

GENES CHROMOSOMES & CANCER, 2016, 55 (08) :626-639

[8]

Clonal evolution in patients with chronic lymphocytic leukaemia developing resistance to BTK inhibition [J].

Burger, Jan A. ;

Landau, Dan A. ;

Taylor-Weiner, Amaro ;

Bozic, Ivana ;

Zhang, Huidan ;

Sarosiek, Kristopher ;

Wang, Lili ;

Stewart, Chip ;

Fan, Jean ;

Hoellenriegel, Julia ;

Sivina, Mariela ;

Dubuc, Adrian M. ;

Fraser, Cameron ;

Han, Yulong ;

Li, Shuqiang ;

Livak, Kenneth J. ;

Zou, Lihua ;

Wan, Youzhong ;

Konoplev, Sergej ;

Sougnez, Carrie ;

Brown, Jennifer R. ;

Abruzzo, Lynne V. ;

Carter, Scott L. ;

Keating, Michael J. ;

Davids, Matthew S. ;

Wierda, William G. ;

Cibulskis, Kristian ;

Zenz, Thorsten ;

Werner, Lillian ;

Dal Cin, Paola ;

Kharchencko, Peter ;

Neuberg, Donna ;

Kantarjian, Hagop ;

Lander, Eric ;

Gabriel, Stacey ;

O'Brien, Susan ;

Letai, Anthony ;

Weitz, David A. ;

Nowak, Martin A. ;

Getz, Gad ;

Wu, Catherine J. .

NATURE COMMUNICATIONS, 2016, 7

[9]

Two main genetic pathways lead to the transformation of chronic lymphocytic leukemia to Richter syndrome [J].

Chigrinova, Ekaterina ;

Rinaldi, Andrea ;

Kwee, Ivo ;

Rossi, Davide ;

Rancoita, Paola M. V. ;

Strefford, Jonathan C. ;

Oscier, David ;

Stamatopoulos, Kostas ;

Papadaki, Theodora ;

Berger, Francoise ;

Young, Ken H. ;

Murray, Fiona ;

Rosenquist, Richard ;

Greiner, Timothy C. ;

Chan, Wing C. ;

Orlandi, Ester M. ;

Lucioni, Marco ;

Marasca, Roberto ;

Inghirami, Giorgio ;

Ladetto, Marco ;

Forconi, Francesco ;

Cogliatti, Sergio ;

Votavova, Hana ;

Swerdlow, Steven H. ;

Stilgenbauer, Stephan ;

Piris, Miguel A. ;

Matolcsy, Andras ;

Spagnolo, Dominic ;

Nikitin, Eugene ;

Zamo, Alberto ;

Gattei, Valter ;

Bhagat, Govind ;

Ott, German ;

Zucca, Emanuele ;

Gaidano, Gianluca ;

Bertoni, Francesco .

BLOOD, 2013, 122 (15) :2673-2682

[10]

Spatial and temporal diversity in genomic instability processes defines lung cancer evolution [J].

de Bruin, Elza C. ;

McGranahan, Nicholas ;

Mitter, Richard ;

Salm, Max ;

Wedge, David C. ;

Yates, Lucy ;

Jamal-Hanjani, Mariam ;

Shafi, Seema ;

Murugaesu, Nirupa ;

Rowan, Andrew J. ;

Groenroos, Eva ;

Muhammad, Madiha A. ;

Horswell, Stuart ;

Gerlinger, Marco ;

Varela, Ignacio ;

Jones, David ;

Marshall, John ;

Voet, Thierry ;

Van Loo, Peter ;

Rassl, Doris M. ;

Rintoul, Robert C. ;

Janes, Sam M. ;

Lee, Siow-Ming ;

Forster, Martin ;

Ahmad, Tanya ;

Lawrence, David ;

Falzon, Mary ;

Capitanio, Arrigo ;

Harkins, Timothy T. ;

Lee, Clarence C. ;

Tom, Warren ;

Teefe, Enock ;

Chen, Shann-Ching ;

Begum, Sharmin ;

Rabinowitz, Adam ;

Phillimore, Benjamin ;

Spencer-Dene, Bradley ;

Stamp, Gordon ;

Szallasi, Zoltan ;

Matthews, Nik ;

Stewart, Aengus ;

Campbell, Peter ;

Swanton, Charles .

SCIENCE, 2014, 346 (6206) :251-256

← 1 2 3 4 →