Genomic landscape of liquid biopsy mutations in TP53 and DNA damage genes in cancer patients

被引：6

作者：

Vasseur, Damien ^{[1
,2
]}

Arbab, Ahmadreza ^{[1
]}

Giudici, Fabiola ^{[3
]}

Marzac, Christophe ^{[1
]}

Michiels, Stefan ^{[3
,4
]}

Tagliamento, Marco ^{[5
]}

Bayle, Arnaud ^{[3
,6
]}

Smolenschi, Cristina ^{[5
,6
]}

Sakkal, Madona ^{[5
,6
]}

Aldea, Mihaela ^{[5
]}

Sassi, Hela ^{[1
]}

Dall'Olio, Filippo Gustavo ^{[5
]}

Pata-Merci, Noemie ^{[2
]}

Cotteret, Sophie ^{[1
]}

Fievet, Alice ^{[1
]}

Auger, Nathalie ^{[1
]}

Friboulet, Luc ^{[7
]}

Facchinetti, Francesco ^{[7
]}

Geraud, Arthur ^{[6
]}

Ponce, Santiago ^{[6
]}

Hollebecque, Antoine ^{[6
]}

Besse, Benjamin ^{[5
,7
]}

Micol, Jean Baptiste ^{[8
]}

Italiano, Antoine ^{[6
]}

Lacroix, Ludovic ^{[1
,2
]}

Rouleau, Etienne ^{[1
,2
]}

机构：

[1] Gustave Roussy, Med Biol & Pathol Dept, F-94805 Villejuif, France

[2] Gustave Roussy, AMMICa UAR3655 US23, F-94805 Villejuif, France

[3] Univ Paris Saclay, Equipe Labellisee Ligue Canc, INSERM, Oncostat U1018, Villejuif, France

[4] Univ Paris Saclay, Bur Biostat & Epidemiol, Gustave Roussy, Villejuif, France

[5] Gustave Roussy, Canc Med, Villejuif, France

[6] Gustave Roussy, Drug Dev Dept DITEP, Villejuif, France

[7] Univ Paris Saclay, Inst Gustave Roussy, Inserm, Biomarqueurs Predict & Nouvelles Strategies Therap, Villejuif, France

[8] Gustave Roussy, Dept Hematol, Villejuif, France

来源：

NPJ PRECISION ONCOLOGY | 2024年 / 8卷 / 01期

关键词：

CLONAL HEMATOPOIESIS; RESISTANCE;

D O I：

10.1038/s41698-024-00544-7

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Next-generation sequencing (NGS) assays based on plasma cell-free DNA (cfDNA) are increasingly used for clinical trials inclusion. Their optimized limit of detection applied to a large number of genes leads to the identification of mutations not confirmed in tissue. It becomes essential to describe the characteristics and consequences of these liquid biopsy-only mutations. In the STING protocol (Gustave Roussy, NCT04932525), 542 patients with advanced solid cancer had cfDNA-based and tissue-based NGS analysis (performed by FoundationOne (R) Liquid CDx and FoundationOne CDx (TM), respectively). Mutations identified in the liquid biopsy but not in the paired tissue were considered as liquid biopsy-only mutations irrespective of their variant allelic frequency (VAF). Out of 542 patients, 281 (51.8%) harbored at least one liquid biopsy-only mutation. These patients were significantly older, and more heavily pretreated. Liquid biopsy-only mutations occurring in TP53, and in DDR genes (ATM, CHEK2, ATR, BRCA2, and BRCA1) accounted for 90.8% of all the mutations. The median VAF of these mutations was generally low (0.37% and 0.40% for TP53 and DDR genes respectively). The variant type repartition depended on the gene. Liquid biopsy-only mutations affected hotspot in TP53 codon 273, 125, 195, 176, 237 or 280 and ATM codon 2891 and 3008. In a subset of 37 patients, 75.0%, 53.5% and 83.3% of the liquid biopsy-only mutations occurring respectively in ATM, TP53, and CHEK2 were confirmed in the matching whole blood sample. Although liquid biopsy-only mutations makes the interpretation of liquid biopsy results more complex, they have distinct characteristics making them more easily identifiable.

引用

页数：10

共 35 条

[1] Non-BRCA DNA Damage Repair Gene Alterations and Response to the PARP Inhibitor Rucaparib in Metastatic Castration-Resistant Prostate Cancer: Analysis From the Phase II TRITON2 Study [J].

Abida, Wassim ;

Campbell, David ;

Patnaik, Akash ;

Shapiro, Jeremy D. ;

Sautois, Brieuc ;

Vogelzang, Nicholas J. ;

Voog, Eric G. ;

Bryce, Alan H. ;

McDermott, Ray ;

Ricci, Francesco ;

Rowe, Julie ;

Zhang, Jingsong ;

Piulats, Josep Maria ;

Fizazi, Karim ;

Merseburger, Axel S. ;

Higano, Celestia S. ;

Krieger, Laurence E. ;

Ryan, Charles J. ;

Feng, Felix Y. ;

Simmons, Andrew D. ;

Loehr, Andrea ;

Despain, Darrin ;

Dowson, Melanie ;

Green, Foad ;

Watkins, Simon P. ;

Golsorkhi, Tony ;

Chowdhury, Simon .

CLINICAL CANCER RESEARCH, 2020, 26 (11) :2487-2496

[2] Clinical Implications of Plasma-Based Genotyping With the Delivery of Personalized Therapy in Metastatic Non-Small Cell Lung Cancer [J].

Aggarwal, Charu ;

Thompson, Jeffrey C. ;

Black, Taylor A. ;

Katz, Sharyn I. ;

Fan, Ryan ;

Yee, Stephanie S. ;

Chien, Austin L. ;

Evans, Tracey L. ;

Bauml, Joshua M. ;

Alley, Evan W. ;

Ciunci, Christine A. ;

Berman, Abigail T. ;

Cohen, Roger B. ;

Lieberman, David B. ;

Majmundar, Krishna S. ;

Savitch, Samantha L. ;

Morrissette, Jennifer J. D. ;

Hwang, Wei-Ting ;

Elenitoba-Johnson, Kojo S. J. ;

Langer, Corey J. ;

Carpenter, Erica L. .

JAMA ONCOLOGY, 2019, 5 (02) :173-180

[3] Detection of additional occult malignancy through profiling of ctDNA in late-stage cancer patients [J].

Aldea, M. ;

Cerbone, L. ;

Bayle, A. ;

Parisi, C. ;

Sarkozy, C. ;

Vasseur, D. ;

Verlingue, L. ;

Blanc-Durand, F. ;

Mosele, F. ;

Sakkal, M. ;

Ponce, S. ;

Lavaud, P. ;

Loriot, Y. ;

Hollebecque, A. ;

Massard, C. ;

Soria, J. -c. ;

Lacroix, L. ;

Rouleau, E. ;

Italiano, A. .

ANNALS OF ONCOLOGY, 2021, 32 (12) :1642-1645

[4] Liquid Biopsies for Circulating Tumor DNA Detection May Reveal Occult Hematologic Malignancies in Patients With Solid Tumors [J].

Aldea, Mihaela ;

Tagliamento, Marco ;

Bayle, Arnaud ;

Vasseur, Damien ;

Verge, Veronique ;

Marinello, Arianna ;

Danlos, Francois-Xavier ;

Blanc-Durand, Felix ;

Bernard, Elsa ;

Cerbone, Luigi ;

Mosele, Maria Fernanda ;

Renneville, Aline ;

Hadoux, Julien ;

Loriot, Yohann ;

Sakkal, Madona ;

Vozy, Aurore ;

Sarkozy, Clementine ;

Smolenschi, Cristina ;

Nicotra, Claudio ;

Martin-Romano, Patricia ;

Boccon-Gibod, Clementine ;

Habza, Wafikaamira ;

Lazarovici, Julien ;

Ponce, Santiago ;

Hollebecque, Antoine ;

Marzac, Christophe ;

Lacroix, Ludovic ;

Barlesi, Fabrice ;

Andre, Fabrice ;

Besse, Benjamin ;

Rouleau, Etienne ;

Italiano, Antoine ;

Micol, Jean-Baptiste .

JCO PRECISION ONCOLOGY, 2023, 7

[5]

Bayle A., 2022, Ann Oncol., Patent No. [S0923753422041473, 0923753422041473]

[6] Detection of Circulating Tumor DNA in Early- and Late-Stage Human Malignancies [J].

Bettegowda, Chetan ;

Sausen, Mark ;

Leary, Rebecca J. ;

Kinde, Isaac ;

Wang, Yuxuan ;

Agrawal, Nishant ;

Bartlett, Bjarne R. ;

Wang, Hao ;

Luber, Brandon ;

Alani, Rhoda M. ;

Antonarakis, Emmanuel S. ;

Azad, Nilofer S. ;

Bardelli, Alberto ;

Brem, Henry ;

Cameron, John L. ;

Lee, Clarence C. ;

Fecher, Leslie A. ;

Gallia, Gary L. ;

Gibbs, Peter ;

Le, Dung ;

Giuntoli, Robert L. ;

Goggins, Michael ;

Hogarty, Michael D. ;

Holdhoff, Matthias ;

Hong, Seung-Mo ;

Jiao, Yuchen ;

Juhl, Hartmut H. ;

Kim, Jenny J. ;

Siravegna, Giulia ;

Laheru, Daniel A. ;

Lauricella, Calogero ;

Lim, Michael ;

Lipson, Evan J. ;

Marie, Suely Kazue Nagahashi ;

Netto, George J. ;

Oliner, Kelly S. ;

Olivi, Alessandro ;

Olsson, Louise ;

Riggins, Gregory J. ;

Sartore-Bianchi, Andrea ;

Schmidt, Kerstin ;

Shih, Ie-Ming ;

Oba-Shinjo, Sueli Mieko ;

Siena, Salvatore ;

Theodorescu, Dan ;

Tie, Jeanne ;

Harkins, Timothy T. ;

Veronese, Silvio ;

Wang, Tian-Li ;

Weingart, Jon D. .

SCIENCE TRANSLATIONAL MEDICINE, 2014, 6 (224)

[7] Cancer therapy shapes the fitness landscape of clonal hematopoiesis [J].

Bolton, Kelly L. ;

Ptashkin, Ryan N. ;

Gao, Teng ;

Braunstein, Lior ;

Devlin, Sean M. ;

Kelly, Daniel ;

Patel, Minal ;

Berthon, Antonin ;

Syed, Aijazuddin ;

Yabe, Mariko ;

Coombs, Catherine C. ;

Caltabellotta, Nicole M. ;

Walsh, Mike ;

Offit, Kenneth ;

Stadler, Zsofia ;

Mandelker, Diana ;

Schulman, Jessica ;

Patel, Akshar ;

Philip, John ;

Bernard, Elsa ;

Gundem, Gunes ;

Ossa, Juan E. Arango ;

Levine, Max ;

Martinez, Juan S. Medina ;

Farnoud, Noushin ;

Glodzik, Dominik ;

Li, Sonya ;

Robson, Mark E. ;

Lee, Choonsik ;

Pharoah, Paul D. P. ;

Stopsack, Konrad H. ;

Spitzer, Barbara ;

Mantha, Simon ;

Fagin, James ;

Boucai, Laura ;

Gibson, Christopher J. ;

Ebert, Benjamin L. ;

Young, Andrew L. ;

Druley, Todd ;

Takahashi, Koichi ;

Gillis, Nancy ;

Ball, Markus ;

Padron, Eric ;

Hyman, David M. ;

Baselga, Jose ;

Norton, Larry ;

Gardos, Stuart ;

Klimek, Virginia M. ;

Scher, Howard ;

Bajorin, Dean .

NATURE GENETICS, 2020, 52 (11) :1219-+

[8] The cBio Cancer Genomics Portal: An Open Platform for Exploring Multidimensional Cancer Genomics Data [J].

Cerami, Ethan ;

Gao, Jianjiong ;

Dogrusoz, Ugur ;

Gross, Benjamin E. ;

Sumer, Selcuk Onur ;

Aksoy, Buelent Arman ;

Jacobsen, Anders ;

Byrne, Caitlin J. ;

Heuer, Michael L. ;

Larsson, Erik ;

Antipin, Yevgeniy ;

Reva, Boris ;

Goldberg, Arthur P. ;

Sander, Chris ;

Schultz, Nikolaus .

CANCER DISCOVERY, 2012, 2 (05) :401-404

[9] Circulating tumour DNA profiling reveals heterogeneity of EGFR inhibitor resistance mechanisms in lung cancer patients [J].

Chabon, Jacob J. ;

Simmons, Andrew D. ;

Lovejoy, Alexander F. ;

Esfahani, Mohammad S. ;

Newman, Aaron M. ;

Haringsma, Henry J. ;

Kurtz, David M. ;

Stehr, Henning ;

Scherer, Florian ;

Karlovich, Chris A. ;

Harding, Thomas C. ;

Durkin, Kathleen A. ;

Otterson, Gregory A. ;

Purcell, W. Thomas ;

Camidge, D. Ross ;

Goldman, Jonathan W. ;

Sequist, Lecia V. ;

Piotrowska, Zofia ;

Wakelee, Heather A. ;

Neal, Joel W. ;

Alizadeh, Ash A. ;

Diehn, Maximilian .

NATURE COMMUNICATIONS, 2016, 7

[10] Mutant p53 drives clonal hematopoiesis through modulating epigenetic pathway [J].

Chen, Sisi ;

Wang, Qiang ;

Yu, Hao ;

Capitano, Maegan L. ;

Vemula, Sasidhar ;

Nabinger, Sarah C. ;

Gao, Rui ;

Yao, Chonghua ;

Kobayashi, Michihiro ;

Geng, Zhuangzhuang ;

Fahey, Aidan ;

Henley, Danielle ;

Liu, Stephen Z. ;

Barajas, Sergio ;

Cai, Wenjie ;

Wolf, Eric R. ;

Ramdas, Baskar ;

Cai, Zhigang ;

Gao, Hongyu ;

Luo, Na ;

Sun, Yang ;

Wong, Terrence N. ;

Link, Daniel C. ;

Liu, Yunlong ;

Boswell, H. Scott ;

Mayo, Lindsey D. ;

Huang, Gang ;

Kapur, Reuben ;

Yoder, Mervin C. ;

Broxmeyer, Hal E. ;

Gao, Zhonghua ;

Liu, Yan .

NATURE COMMUNICATIONS, 2019, 10 (1)

← 1 2 3 4 →