The genomic landscape of metastatic clear cell renal cell carcinoma after systemic therapy

被引：7

作者：

van der Mijn, Johannes C. ^{[1
,2
,3
]}

Eng, Kenneth W. ^{[3
,4
,5
]}

Chandra, Pooja ^{[3
,4
,5
]}

Fernandez, Evan ^{[3
,4
,5
]}

Ramazanoglu, Sinan ^{[3
,4
,5
]}

Sigaras, Alexandros ^{[3
,4
,5
]}

Oromendia, Clara ^{[1
]}

Gudas, Lorraine J. ^{[1
]}

Tagawa, Scott T. ^{[3
,6
]}

Nanus, David M. ^{[3
,6
]}

Faltas, Bishoy F. ^{[3
,6
]}

Beltran, Himisha ^{[3
,6
]}

Sternberg, Cora N. ^{[3
,6
]}

Elemento, Olivier ^{[3
,4
,5
]}

Sboner, Andrea ^{[3
,4
,7
]}

Mosquera, Juan Miguel ^{[3
,7
]}

Molina, Ana M. ^{[3
,6
]}

机构：

[1] Weill Cornell Med, Dept Pharmacol, New York, NY 10021 USA

[2] Netherlands Canc Inst NKI, Dept Med Oncol, Amsterdam, Netherlands

[3] Weill Cornell Med, Englander Inst Precis Med, New York, NY 10021 USA

[4] Weill Cornell Med, Inst Computat Biomed, New York, NY 10021 USA

[5] Weill Cornell Med, Dept Physiol & Biophys, New York, NY 10021 USA

[6] Weill Cornell Med, Div Hematol Oncol, Dept Med, 520 East 70th St, New York, NY 10021 USA

[7] Weill Cornell Med, Dept Pathol & Lab Med, New York, NY 10021 USA

来源：

MOLECULAR ONCOLOGY | 2022年 / 16卷 / 12期

关键词：

cancer; genomics; immunotherapy; kidney; metastasis; VEGF; BIOMARKERS; CANCER; HETEROGENEITY; EXPRESSION; EVOLUTION; GENE;

D O I：

10.1002/1878-0261.13204

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Primary clear cell renal cell carcinoma (ccRCC) has been previously characterized, but the genomic landscape of metastatic ccRCC is largely unexplored. Here, we performed whole exome sequencing (WES) in 68 samples from 44 patients with ccRCC, including 52 samples from a metastatic site. SETD2, PBRM1, APC and VHL were the most frequently mutated genes in the metastatic ccRCC cohort. RBM10 and FBXW7 were also among the 10 most frequently mutated genes in metastatic tissues. Recurrent somatic copy number variations (CNV) were observed at the previously identified regions 3p25, 9p21 and 14q25, but also at 6p21 (CDKN1A) and 13q14 (RB1). No statistically significant differences were found between samples from therapy-naive and pretreated patients. Clonal evolution analyses with multiple samples from 13 patients suggested that early appearance of CNVs at 3p25, 9p21 and 14q25 may be associated with rapid clinical progression. Overall, the genomic landscapes of primary and metastatic ccRCC seem to share frequent CNVs at 3p25, 9p21 and 14q25. Future work will clarify the implication of RBM10 and FBXW7 mutations and 6p21 and 13q14 CNVs in metastatic ccRCC.

引用

页码：2384 / 2395

页数：12

共 38 条

[1] Determinants of anti-PD-1 response and resistance in clear cell renal cell carcinoma [J].

Au, Lewis ;

Hatipoglu, Emine ;

de Massy, Marc Robert ;

Litchfield, Kevin ;

Beattie, Gordon ;

Rowan, Andrew ;

Schnidrig, Desiree ;

Thompson, Rachael ;

Byrne, Fiona ;

Horswell, Stuart ;

Fotiadis, Nicos ;

Hazell, Steve ;

Nicol, David ;

Shepherd, Scott T. C. ;

Fendler, Annika ;

Mason, Robert ;

Del Rosario, Lyra ;

Edmonds, Kim ;

Lingard, Karla ;

Sarker, Sarah ;

Mangwende, Mary ;

Carlyle, Eleanor ;

Attig, Jan ;

Joshi, Kroopa ;

Uddin, Imran ;

Becker, Pablo D. ;

Sunderland, Mariana Werner ;

Akarca, Ayse ;

Puccio, Ignazio ;

Yang, William W. ;

Lund, Tom ;

Dhillon, Kim ;

Vasquez, Marcos Duran ;

Ghorani, Ehsan ;

Xu, Hang ;

Spencer, Charlotte ;

Lopez, Jose, I ;

Green, Anna ;

Mahadeva, Ula ;

Borg, Elaine ;

Mitchison, Miriam ;

Moore, David A. ;

Proctor, Ian ;

Falzon, Mary ;

Pickering, Lisa ;

Furness, Andrew J. S. ;

Reading, James L. ;

Salgado, Roberto ;

Marafioti, Teresa ;

Jamal-Hanjani, Mariam .

CANCER CELL, 2021, 39 (11) :1497-+

[2] Influence of Chemotherapy on EGFR Mutation Status Among Patients With Non-Small-Cell Lung Cancer [J].

Bai, Hua ;

Wang, Zhijie ;

Chen, Keneng ;

Zhao, Jun ;

Lee, J. Jack ;

Wang, Shuhang ;

Zhou, Qinghua ;

Zhuo, Minglei ;

Mao, Li ;

An, Tongtong ;

Duan, Jianchun ;

Yang, Lu ;

Wu, Meina ;

Liang, Zhen ;

Wang, Yuyan ;

Kang, Xiaozheng ;

Wang, Jie .

JOURNAL OF CLINICAL ONCOLOGY, 2012, 30 (25) :3077-3083

[3] Comparative Genomic Profiling of Matched Primary and Metastatic Tumors in Renal Cell Carcinoma [J].

Becerra, Maria F. ;

Reznik, Ed ;

Redzematovic, Almedina ;

Tennenbaum, Daniel M. ;

Kashan, Mahyar ;

Ghanaat, Mazyar ;

Casuscelli, Jozefina ;

Manley, Brandon ;

Jonsson, Philip ;

DiNatale, Renzo G. ;

Blum, Kyle A. ;

Durack, Jeremy C. ;

Solomon, Stephen B. ;

Arcila, Maria E. ;

Bourque, Caitlin ;

Socci, Nick ;

Carlo, Maria I. ;

Lee, Chung-Han ;

Voss, Martin H. ;

Feldman, Darren R. ;

Motzer, Robert J. ;

Coleman, Jonathan A. ;

Russo, Paul ;

Cheng, Emily H. ;

Hakimi, A. Ari ;

Hsieh, James J. .

EUROPEAN UROLOGY FOCUS, 2018, 4 (06) :986-994

[4] Whole-Exome Sequencing of Metastatic Cancer and Biomarkers of Treatment Response [J].

Beltran, Himisha ;

Eng, Kenneth ;

Mosquera, Juan Miguel ;

Sigaras, Alexandros ;

Romanel, Alessandro ;

Rennert, Hanna ;

Kossai, Myriam ;

Pauli, Chantal ;

Faltas, Bishoy ;

Fontugne, Jacqueline ;

Park, Kyung ;

Banfelder, Jason ;

Prandi, Davide ;

Madhukar, Neel ;

Zhang, Tuo ;

Padilla, Jessica ;

Greco, Noah ;

McNary, Terra J. ;

Herrscher, Erick ;

Wilkes, David ;

MacDonald, Theresa Y. ;

Xue, Hui ;

Vacic, Vladimir ;

Emde, Anne-Katrin ;

Oschwald, Dayna ;

Tan, Adrian Y. ;

Chen, Zhengming ;

Collins, Colin ;

Gleave, Martin E. ;

Wang, Yuzhuo ;

Chakravarty, Dimple ;

Schiffman, Marc ;

Kim, Robert ;

Campagne, Fabien ;

Robinson, Brian D. ;

Nanus, David M. ;

Tagawa, Scott T. ;

Xiang, Jenny Z. ;

Smogorzewska, Agata ;

Demichelis, Francesca ;

Rickman, David S. ;

Sboner, Andrea ;

Elemento, Olivier ;

Rubin, Mark A. .

JAMA ONCOLOGY, 2015, 1 (04) :466-474

[5] Patterns of Gene Expression and Copy-Number Alterations in von-Hippel Lindau Disease-Associated and Sporadic Clear Cell Carcinoma of the Kidney [J].

Beroukhim, Rameen ;

Brunet, Jean-Philippe ;

Di Napoli, Arianna ;

Mertz, Kirsten D. ;

Seeley, Apryle ;

Pires, Maira M. ;

Linhart, David ;

Worrell, Robert A. ;

Moch, Holger ;

Rubin, Mark A. ;

Sellers, William R. ;

Meyerson, Matthew ;

Linehan, W. Marston ;

Kaelin, William G., Jr. ;

Signoretti, Sabina .

CANCER RESEARCH, 2009, 69 (11) :4674-4681

[6] Tumor and immune reprogramming during immunotherapy in advanced renal cell carcinoma [J].

Bi, Kevin ;

He, Meng Xiao ;

Bakouny, Ziad ;

Kanodia, Abhay ;

Napolitano, Sara ;

Wu, Jingyi ;

Grimaldi, Grace ;

Braun, David A. ;

Cuoco, Michael S. ;

Mayorga, Angie ;

DelloStritto, Laura ;

Bouchard, Gabrielle ;

Steinharter, John ;

Tewari, Alok K. ;

Vokes, Natalie, I ;

Shannon, Erin ;

Sun, Maxine ;

Park, Jihye ;

Chang, Steven L. ;

McGregor, Bradley A. ;

Haq, Rizwan ;

Denize, Thomas ;

Signoretti, Sabina ;

Guerriero, Jennifer L. ;

Vigneau, Sebastien ;

Rozenblatt-Rosen, Orit ;

Rotem, Asaf ;

Regev, Aviv ;

Choueiri, Toni K. ;

Van Allen, Eliezer M. .

CANCER CELL, 2021, 39 (05) :649-+

[7] Beyond conventional immune-checkpoint inhibition - novel immunotherapies for renal cell carcinoma [J].

Braun, David A. ;

Bakouny, Ziad ;

Hirsch, Laure ;

Flippot, Ronan ;

Van Allen, Eliezer M. ;

Wu, Catherine J. ;

Choueiri, Toni K. .

NATURE REVIEWS CLINICAL ONCOLOGY, 2021, 18 (04) :199-214

[8] Interplay of somatic alterations and immune infiltration modulates response to PD-1 blockade in advanced clear cell renal cell carcinoma [J].

Braun, David A. ;

Hou, Yue ;

Bakouny, Ziad ;

Ficial, Miriam ;

Sant' Angelo, Miriam ;

Forman, Juliet ;

Ross-Macdonald, Petra ;

Berger, Ashton C. ;

Jegede, Opeyemi A. ;

Elagina, Liudmilla ;

Steinharter, John ;

Sun, Maxine ;

Wind-Rotolo, Megan ;

Pignon, Jean-Christophe ;

Cherniack, Andrew D. ;

Lichtenstein, Lee ;

Neuberg, Donna ;

Catalano, Paul ;

Freeman, Gordon J. ;

Sharpe, Arlene H. ;

McDermott, David F. ;

Van Allen, Eliezer M. ;

Signoretti, Sabina ;

Wu, Catherine J. ;

Shukla, Sachet A. ;

Choueiri, Toni K. .

NATURE MEDICINE, 2020, 26 (06) :909-+

[9] Comprehensivemolecular characterization of clear cell renal cell carcinoma [J].

Creighton, Chad J. ;

Morgan, Margaret ;

Gunaratne, Preethi H. ;

Wheeler, David A. ;

Gibbs, Richard A. ;

Robertson, A. Gordon ;

Chu, Andy ;

Beroukhim, Rameen ;

Cibulskis, Kristian ;

Signoretti, Sabina ;

Vandin, Fabio ;

Wu, Hsin-Ta ;

Raphael, Benjamin J. ;

Verhaak, Roel G. W. ;

Tamboli, Pheroze ;

Torres-Garcia, Wandaliz ;

Akbani, Rehan ;

Weinstein, John N. ;

Reuter, Victor ;

Hsieh, James J. ;

Brannon, A. Rose ;

Hakimi, A. Ari ;

Jacobsen, Anders ;

Ciriello, Giovanni ;

Reva, Boris ;

Ricketts, Christopher J. ;

Linehan, W. Marston ;

Stuart, Joshua M. ;

Rathmell, W. Kimryn ;

Shen, Hui ;

Laird, Peter W. ;

Muzny, Donna ;

Davis, Caleb ;

Morgan, Margaret ;

Xi, Liu ;

Chang, Kyle ;

Kakkar, Nipun ;

Trevino, Lisa R. ;

Benton, Susan ;

Reid, Jeffrey G. ;

Morton, Donna ;

Doddapaneni, Harsha ;

Han, Yi ;

Lewis, Lora ;

Dinh, Huyen ;

Kovar, Christie ;

Zhu, Yiming ;

Santibanez, Jireh ;

Wang, Min ;

Hale, Walker .

NATURE, 2013, 499 (7456) :43-+

[10] Targeted genomic landscape of metastases compared to primary tumours in clear cell metastatic renal cell carcinoma [J].

de Velasco, Guillermo ;

Wankowicz, Stephanie A. ;

Madison, Russell ;

Ali, Siraj M. ;

Norton, Craig ;

Duquette, Audrey ;

Ross, Jeffrey S. ;

Bosse, Dominick ;

Lalani, Aly-Khan A. ;

Miller, Vincent A. ;

Stephens, Philip J. ;

Young, Lauren ;

Hakimi, A. Ari ;

Signoretti, Sabina ;

Pal, Sumanta K. ;

Choueiri, Toni K. .

BRITISH JOURNAL OF CANCER, 2018, 118 (09) :1238-1242

← 1 2 3 4 →