A transcriptomic model for homologous recombination deficiency in prostate cancer

被引：13

作者：

Weiner, Adam B. ^{[1
]}

Liu, Yang ^{[2
]}

McFarlane, Matthew ^{[3
]}

Bawa, Pushpinder S. ^{[4
]}

Li, Eric, V ^{[1
]}

Zhao, Xin ^{[2
]}

Li, Ziwen ^{[2
]}

Hammoud, Tanya ^{[5
]}

Hazime, Munna ^{[5
]}

Karnes, R. Jeffrey ^{[6
]}

Davicioni, Elai ^{[2
]}

Reichert, Zachery R. ^{[7
]}

Chinnaiyan, Arul M. ^{[4
]}

Lotan, Tamara L. ^{[8
]}

Spratt, Daniel E. ^{[3
]}

Schaeffer, Edward M. ^{[1
]}

机构：

[1] Northwestern Univ, Dept Urol, Feinberg Sch Med, Chicago, IL 60208 USA

[2] Decipher Biosci, San Diego, CA USA

[3] Univ Michigan, Dept Radiat Oncol, Ann Arbor, MI 48109 USA

[4] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA

[5] Univ Michigan, Coll Literature Sci & Arts, Ann Arbor, MI USA

[6] Mayo Clin, Dept Urol, Rochester, MN USA

[7] Univ Michigan, Div Hematol Oncol, Dept Internal Med, Rogel Comprehens Canc Ctr, Ann Arbor, MI USA

[8] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA

来源：

PROSTATE CANCER AND PROSTATIC DISEASES | 2022年 / 25卷 / 04期

基金：

美国国家卫生研究院;

关键词：

MOLECULAR SIGNATURES; DNA-REPAIR; CELL-CYCLE; CHEMOTHERAPY; MUTATIONS; BRCANESS; BRCA1; RISK;

D O I：

10.1038/s41391-021-00416-2

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background Tumors with mutations associated with homologous recombination deficiency (HRD) are uncommon in prostate cancer (PCa) and variably responsive to PARP inhibition. To better identify tumors with HRD, we developed a transcriptomic signature for HRD in PCa (HRD-P). Methods By using an established mutational signature, we created and validated HRD-P in six independent PCa cohorts (primary PCa, n = 8224; metastatic castration-resistant PCa [mCRPC], n = 328). Molecular and clinical features were compared between HRD-P+ tumors and those with single HR-gene mutations. Results HRD-P+ tumors were more common than tumors with single HR-gene mutations in primary (201/491, 41% vs 32/491 6.5%) and mCRPC (126/328, 38% vs 82/328, 25%) cases, and HRD-P+ was more predictive of genomic instability suggestive of HRD. HRD-P+ was associated with a shorter time to recurrence following surgery and shorter overall survival in men with mCRPC. In a prospective trial of mCRPC treated with olaparib (n = 10), all three men with HRD-P+ experienced prolonged (>330 days) PSA progression-free survival. Conclusion These results suggest transcriptomics can identify more patients that harbor phenotypic HRD than single HR-gene mutations and support further exploration of transcriptionally defined HRD tumors perhaps in conjunction with genomic markers for therapeutic application.

引用

页码：659 / 665

页数：7

共 31 条

[1] The Molecular Taxonomy of Primary Prostate Cancer [J].

Abeshouse, Adam ;

Ahn, Jaeil ;

Akbani, Rehan ;

Ally, Adrian ;

Amin, Samirkumar ;

Andry, Christopher D. ;

Annala, Matti ;

Aprikian, Armen ;

Armenia, Joshua ;

Arora, Arshi ;

Auman, J. Todd ;

Balasundaram, Miruna ;

Balu, Saianand ;

Barbieri, Christopher E. ;

Bauer, Thomas ;

Benz, Christopher C. ;

Bergeron, Alain ;

Beroukhim, Rameen ;

Berrios, Mario ;

Bivol, Adrian ;

Bodenheimer, Tom ;

Boice, Lori ;

Bootwalla, Moiz S. ;

dos Reis, Rodolfo Borges ;

Boutros, Paul C. ;

Bowen, Jay ;

Bowlby, Reanne ;

Boyd, Jeffrey ;

Bradley, Robert K. ;

Breggia, Anne ;

Brimo, Fadi ;

Bristow, Christopher A. ;

Brooks, Denise ;

Broom, Bradley M. ;

Bryce, Alan H. ;

Bubley, Glenn ;

Burks, Eric ;

Butterfield, Yaron S. N. ;

Button, Michael ;

Canes, David ;

Carlotti, Carlos G. ;

Carlsen, Rebecca ;

Carmel, Michel ;

Carroll, Peter R. ;

Carter, Scott L. ;

Cartun, Richard ;

Carver, Brett S. ;

Chan, June M. ;

Chang, Matthew T. ;

Chen, Yu .

CELL, 2015, 163 (04) :1011-1025

[2] Rucaparib in Men With Metastatic Castration-Resistant Prostate Cancer Harboring a BRCA1 or BRCA2 Gene Alteration [J].

Abida, Wassim ;

Patnaik, Akash ;

Campbell, David ;

Shapiro, Jeremy ;

Bryce, Alan H. ;

McDermott, Ray ;

Sautois, Brieuc ;

Vogelzang, Nicholas J. ;

Bambury, Richard M. ;

Voog, Eric ;

Zhang, Jingsong ;

Piulats, Josep M. ;

Ryan, Charles J. ;

Merseburger, Axel S. ;

Daugaard, Gedske ;

Heidenreich, Axel ;

Fizazi, Karim ;

Higano, Celestia S. ;

Krieger, Laurence E. ;

Sternberg, Cora N. ;

Watkins, Simon P. ;

Despain, Darrin ;

Simmons, Andrew D. ;

Loehr, Andrea ;

Dowson, Melanie ;

Golsorkhi, Tony ;

Chowdhury, Simon .

JOURNAL OF CLINICAL ONCOLOGY, 2020, 38 (32) :3763-+

[3] Genomic correlates of clinical outcome in advanced prostate cancer [J].

Abida, Wassim ;

Cyrta, Joanna ;

Heller, Glenn ;

Prandi, Davide ;

Armenia, Joshua ;

Coleman, Ilsa ;

Cieslik, Marcin ;

Benelli, Matteo ;

Robinson, Dan ;

Van Allen, Eliezer M. ;

Sboner, Andrea ;

Fedrizzi, Tarcisio ;

Mosquera, Juan Miguel ;

Robinson, Brian D. ;

De Sarkar, Navonil ;

Kunju, Lakshmi P. ;

Tomlins, Scott ;

Wu, Yi Mi ;

Rodrigues, Daniel Nava ;

Loda, Massimo ;

Gopalan, Anuradha ;

Reuter, Victor E. ;

Pritchard, Colin C. ;

Mateo, Joaquin ;

Bianchini, Diletta ;

Miranda, Susana ;

Carreira, Suzanne ;

Rescigno, Pasquale ;

Filipenko, Julie ;

Vinson, Jacob ;

Montgomery, Robert B. ;

Beltran, Himisha ;

Heath, Elisabeth I. ;

Scher, Howard I. ;

Kantoff, Philip W. ;

Taplin, Mary-Ellen ;

Schultz, Nikolaus ;

deBono, Johann S. ;

Demichelis, Francesca ;

Nelson, Peter S. ;

Rubin, Mark A. ;

Chinnaiyan, Arul M. ;

Sawyers, Charles L. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2019, 116 (23) :11428-11436

[4] PROREPAIR-B: A Prospective Cohort Study of the Impact of Germline DNA Repair Mutations on the Outcomes of Patients With Metastatic Castration-Resistant Prostate Cancer [J].

Castro, Elena ;

Romero-Laorden, Nuria ;

del Pozo, Angela ;

Lozano, Rebeca ;

Medina, Ana ;

Puente, Javier ;

Maria Piulats, Josep ;

Lorente, David ;

Isabel Saez, Maria ;

Morales-Barrera, Rafael ;

Gonzalez-Billalabeitia, Enrique ;

Cendon, Ylenia ;

Garcia-Carbonero, Iciar ;

Borrega, Pablo ;

Mendez Vidal, M. Jose ;

Montesa, Alvaro ;

Nombela, Paz ;

Fernandez-Parra, Eva ;

Gonzalez del Alba, Aranzazu ;

Carlos Villa-Guzman, Jose ;

Ibanez, Kristina ;

Rodriguez-Vida, Alejo ;

Magraner-Pardo, Lorena ;

Perez-Valderrama, Begona ;

Vallespin, Elena ;

Gallardo, Enrique ;

Vazquez, Sergio ;

Pritchard, Colin C. ;

Lapunzina, Pablo ;

Olmos, David .

JOURNAL OF CLINICAL ONCOLOGY, 2019, 37 (06) :490-+

[5] Effect of BRCA Mutations on Metastatic Relapse and Cause-specific Survival After Radical Treatment for Localised Prostate Cancer [J].

Castro, Elena ;

Goh, Chee ;

Leongamornlert, Daniel ;

Saunders, Ed ;

Tymrakiewicz, Malgorzata ;

Dadaev, Tokhir ;

Govindasami, Koveela ;

Guy, Michelle ;

Ellis, Steve ;

Frost, Debra ;

Bancroft, Elizabeth ;

Cole, Trevor ;

Tischkowitz, Marc ;

Kennedy, M. John ;

Eason, Jacqueline ;

Brewer, Carole ;

Evans, D. Gareth ;

Davidson, Rosemarie ;

Eccles, Diana ;

Porteous, Mary E. ;

Douglas, Fiona ;

Adlard, Julian ;

Donaldson, Alan ;

Antoniou, Antonis C. ;

Kote-Jarai, Zsofia ;

Easton, Douglas F. ;

Olmos, David ;

Eeles, Rosalind .

EUROPEAN UROLOGY, 2015, 68 (02) :186-193

[6] 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

[7] HRDetect is a predictor of BRCA1 and BRCA2 deficiency based on mutational signatures [J].

Davies, Helen ;

Glodzik, Dominik ;

Morganella, Sandro ;

Yates, Lucy R. ;

Staaf, Johan ;

Zou, Xueqing ;

Ramakrishna, Manasa ;

Martin, Sancha ;

Boyault, Sandrine ;

Sieuwerts, Anieta M. ;

Simpson, Peter T. ;

King, Tari A. ;

Raine, Keiran ;

Eyfjord, Jorunn E. ;

Kong, Gu ;

Borg, Ake ;

Birney, Ewan ;

Stunnenberg, Hendrik G. ;

van de Vijver, Marc J. ;

Borresen-Dale, Anne-Lise ;

Martens, John W. M. ;

Span, Paul N. ;

Lakhani, Sunil R. ;

Vincent-Salomon, Anne ;

Sotiriou, Christos ;

Tutt, Andrew ;

Thompson, Alastair M. ;

Van Laere, Steven ;

Richardson, Andrea L. ;

Viari, Alain ;

Campbell, Peter J. ;

Stratton, Michael R. ;

Nik-Zainal, Serena .

NATURE MEDICINE, 2017, 23 (04) :517-+

[8] Olaparib for Metastatic Castration-Resistant Prostate Cancer [J].

de Bono, J. ;

Mateo, J. ;

Fizazi, K. ;

Saad, F. ;

Shore, N. ;

Sandhu, S. ;

Chi, K. N. ;

Sartor, O. ;

Agarwal, N. ;

Olmos, D. ;

Thiery-Vuillemin, A. ;

Twardowski, P. ;

Mehra, N. ;

Goessl, C. ;

Kang, J. ;

Burgents, J. ;

Wu, W. ;

Kohlmann, A. ;

Adelman, C. A. ;

Hussain, M. .

NEW ENGLAND JOURNAL OF MEDICINE, 2020, 382 (22) :2091-2102

[9] Integrative Analysis of Complex Cancer Genomics and Clinical Profiles Using the cBioPortal [J].

Gao, Jianjiong ;

Aksoy, Buelent Arman ;

Dogrusoz, Ugur ;

Dresdner, Gideon ;

Gross, Benjamin ;

Sumer, S. Onur ;

Sun, Yichao ;

Jacobsen, Anders ;

Sinha, Rileen ;

Larsson, Erik ;

Cerami, Ethan ;

Sander, Chris ;

Schultz, Nikolaus .

SCIENCE SIGNALING, 2013, 6 (269) :pl1

[10]

Hastie T., 2001, The Elements of Statistical learning: Data Mining, Inference, and Prediction, P41, DOI [DOI 10.1007/978, 10.1007/978-0-387-21606-5]_3]

← 1 2 3 4 →