Integrative clinical genomics of advanced prostate cancer

Dan Robinson; Eliezer M. Van Allen; Yi Mi Wu; Nikolaus Schultz; Robert J. Lonigro; Juan Miguel Mosquera; Bruce Montgomery; Mary Ellen Taplin; Colin C. Pritchard; Gerhardt Attard; Himisha Beltran; Wassim Abida; Robert K. Bradley; Jake Vinson; Xuhong Cao; Pankaj Vats; Lakshmi P. Kunju; Maha Hussain; Felix Y. Feng; Scott A. Tomlins; Kathleen A. Cooney; David C. Smith; Christine Brennan; Javed Siddiqui; Rohit Mehra; Yu Chen; Dana E. Rathkopf; Michael J. Morris; Stephen B. Solomon; Jeremy C. Durack; Victor E. Reuter; Anuradha Gopalan; Jianjiong Gao; Massimo Loda; Rosina T. Lis; Michaela Bowden; Stephen P. Balk; Glenn Gaviola; Carrie Sougnez; Manaswi Gupta; Evan Y. Yu; Elahe A. Mostaghel; Heather H. Cheng; Hyojeong Mulcahy; Lawrence D. True; Stephen R. Plymate; Heidi Dvinge; Roberta Ferraldeschi; Penny Flohr; Susana Miranda; Zafeiris Zafeiriou; Nina Tunariu; Joaquin Mateo; Raquel Perez-Lopez; Francesca Demichelis; Brian D. Robinson; Marc Schiffman; David M. Nanus; Scott T. Tagawa; Alexandros Sigaras; Kenneth W. Eng; Olivier Elemento; Andrea Sboner; Elisabeth I. Heath; Howard I. Scher; Kenneth J. Pienta; Philip Kantoff; Johann S. De Bono; Mark A. Rubin; Peter S. Nelson; Levi A. Garraway; Charles L. Sawyers; Arul M. Chinnaiyan

doi:10.1016/j.cell.2015.05.001

Integrative clinical genomics of advanced prostate cancer

Dan Robinson, Eliezer M. Van Allen, Yi Mi Wu, Nikolaus Schultz, Robert J. Lonigro, Juan Miguel Mosquera, Bruce Montgomery, Mary Ellen Taplin, Colin C. Pritchard, Gerhardt Attard, Himisha Beltran, Wassim Abida, Robert K. Bradley, Jake Vinson, Xuhong Cao, Pankaj Vats, Lakshmi P. Kunju, Maha Hussain, Felix Y. Feng, Scott A. TomlinsKathleen A. Cooney, David C. Smith, Christine Brennan, Javed Siddiqui, Rohit Mehra, Yu Chen, Dana E. Rathkopf, Michael J. Morris, Stephen B. Solomon, Jeremy C. Durack, Victor E. Reuter, Anuradha Gopalan, Jianjiong Gao, Massimo Loda, Rosina T. Lis, Michaela Bowden, Stephen P. Balk, Glenn Gaviola, Carrie Sougnez, Manaswi Gupta, Evan Y. Yu, Elahe A. Mostaghel, Heather H. Cheng, Hyojeong Mulcahy, Lawrence D. True, Stephen R. Plymate, Heidi Dvinge, Roberta Ferraldeschi, Penny Flohr, Susana Miranda, Zafeiris Zafeiriou, Nina Tunariu, Joaquin Mateo, Raquel Perez-Lopez, Francesca Demichelis, Brian D. Robinson, Marc Schiffman, David M. Nanus, Scott T. Tagawa, Alexandros Sigaras, Kenneth W. Eng, Olivier Elemento, Andrea Sboner, Elisabeth I. Heath, Howard I. Scher, Kenneth J. Pienta, Philip Kantoff, Johann S. De Bono, Mark A. Rubin, Peter S. Nelson, Levi A. Garraway, Charles L. Sawyers, Arul M. Chinnaiyan

School of Medicine

Research output: Contribution to journal › Article › peer-review

1508 Scopus citations

Abstract

Toward development of a precision medicine framework for metastatic, castration-resistant prostate cancer (mCRPC), we established a multi-institutional clinical sequencing infrastructure to conduct prospective whole-exome and transcriptome sequencing of bone or soft tissue tumor biopsies from a cohort of 150 mCRPC affected individuals. Aberrations of AR, ETS genes, TP53, and PTEN were frequent (40%-60% of cases), with TP53 and AR alterations enriched in mCRPC compared to primary prostate cancer. We identified new genomic alterations in PIK3CA/B, R-spondin, BRAF/RAF1, APC, β-catenin, and ZBTB16/PLZF. Moreover, aberrations of BRCA2, BRCA1, and ATM were observed at substantially higher frequencies (19.3% overall) compared to those in primary prostate cancers. 89% of affected individuals harbored a clinically actionable aberration, including 62.7% with aberrations in AR, 65% in other cancer-related genes, and 8% with actionable pathogenic germline alterations. This cohort study provides clinically actionable information that could impact treatment decisions for these affected individuals.

Original language	English (US)
Pages (from-to)	1215-1228
Number of pages	14
Journal	Cell
Volume	161
Issue number	5
DOIs	https://doi.org/10.1016/j.cell.2015.05.001
State	Published - May 30 2015

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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Robinson, D., Van Allen, E. M., Wu, Y. M., Schultz, N., Lonigro, R. J., Mosquera, J. M., Montgomery, B., Taplin, M. E., Pritchard, C. C., Attard, G., Beltran, H., Abida, W., Bradley, R. K., Vinson, J., Cao, X., Vats, P., Kunju, L. P., Hussain, M., Feng, F. Y., ... Chinnaiyan, A. M. (2015). Integrative clinical genomics of advanced prostate cancer. Cell, 161(5), 1215-1228. https://doi.org/10.1016/j.cell.2015.05.001

Robinson, D, Van Allen, EM, Wu, YM, Schultz, N, Lonigro, RJ, Mosquera, JM, Montgomery, B, Taplin, ME, Pritchard, CC, Attard, G, Beltran, H, Abida, W, Bradley, RK, Vinson, J, Cao, X, Vats, P, Kunju, LP, Hussain, M, Feng, FY, Tomlins, SA, Cooney, KA, Smith, DC, Brennan, C, Siddiqui, J, Mehra, R, Chen, Y, Rathkopf, DE, Morris, MJ, Solomon, SB, Durack, JC, Reuter, VE, Gopalan, A, Gao, J, Loda, M, Lis, RT, Bowden, M, Balk, SP, Gaviola, G, Sougnez, C, Gupta, M, Yu, EY, Mostaghel, EA, Cheng, HH, Mulcahy, H, True, LD, Plymate, SR, Dvinge, H, Ferraldeschi, R, Flohr, P, Miranda, S, Zafeiriou, Z, Tunariu, N, Mateo, J, Perez-Lopez, R, Demichelis, F, Robinson, BD, Schiffman, M, Nanus, DM, Tagawa, ST, Sigaras, A, Eng, KW, Elemento, O, Sboner, A, Heath, EI, Scher, HI, Pienta, KJ, Kantoff, P, De Bono, JS, Rubin, MA, Nelson, PS, Garraway, LA, Sawyers, CL & Chinnaiyan, AM 2015, 'Integrative clinical genomics of advanced prostate cancer', Cell, vol. 161, no. 5, pp. 1215-1228. https://doi.org/10.1016/j.cell.2015.05.001

@article{cb7d17d5ea5d4f6f9f59b127a41ad338,

title = "Integrative clinical genomics of advanced prostate cancer",

abstract = "Toward development of a precision medicine framework for metastatic, castration-resistant prostate cancer (mCRPC), we established a multi-institutional clinical sequencing infrastructure to conduct prospective whole-exome and transcriptome sequencing of bone or soft tissue tumor biopsies from a cohort of 150 mCRPC affected individuals. Aberrations of AR, ETS genes, TP53, and PTEN were frequent (40%-60% of cases), with TP53 and AR alterations enriched in mCRPC compared to primary prostate cancer. We identified new genomic alterations in PIK3CA/B, R-spondin, BRAF/RAF1, APC, β-catenin, and ZBTB16/PLZF. Moreover, aberrations of BRCA2, BRCA1, and ATM were observed at substantially higher frequencies (19.3% overall) compared to those in primary prostate cancers. 89% of affected individuals harbored a clinically actionable aberration, including 62.7% with aberrations in AR, 65% in other cancer-related genes, and 8% with actionable pathogenic germline alterations. This cohort study provides clinically actionable information that could impact treatment decisions for these affected individuals.",

author = "Dan Robinson and {Van Allen}, {Eliezer M.} and Wu, {Yi Mi} and Nikolaus Schultz and Lonigro, {Robert J.} and Mosquera, {Juan Miguel} and Bruce Montgomery and Taplin, {Mary Ellen} and Pritchard, {Colin C.} and Gerhardt Attard and Himisha Beltran and Wassim Abida and Bradley, {Robert K.} and Jake Vinson and Xuhong Cao and Pankaj Vats and Kunju, {Lakshmi P.} and Maha Hussain and Feng, {Felix Y.} and Tomlins, {Scott A.} and Cooney, {Kathleen A.} and Smith, {David C.} and Christine Brennan and Javed Siddiqui and Rohit Mehra and Yu Chen and Rathkopf, {Dana E.} and Morris, {Michael J.} and Solomon, {Stephen B.} and Durack, {Jeremy C.} and Reuter, {Victor E.} and Anuradha Gopalan and Jianjiong Gao and Massimo Loda and Lis, {Rosina T.} and Michaela Bowden and Balk, {Stephen P.} and Glenn Gaviola and Carrie Sougnez and Manaswi Gupta and Yu, {Evan Y.} and Mostaghel, {Elahe A.} and Cheng, {Heather H.} and Hyojeong Mulcahy and True, {Lawrence D.} and Plymate, {Stephen R.} and Heidi Dvinge and Roberta Ferraldeschi and Penny Flohr and Susana Miranda and Zafeiris Zafeiriou and Nina Tunariu and Joaquin Mateo and Raquel Perez-Lopez and Francesca Demichelis and Robinson, {Brian D.} and Marc Schiffman and Nanus, {David M.} and Tagawa, {Scott T.} and Alexandros Sigaras and Eng, {Kenneth W.} and Olivier Elemento and Andrea Sboner and Heath, {Elisabeth I.} and Scher, {Howard I.} and Pienta, {Kenneth J.} and Philip Kantoff and {De Bono}, {Johann S.} and Rubin, {Mark A.} and Nelson, {Peter S.} and Garraway, {Levi A.} and Sawyers, {Charles L.} and Chinnaiyan, {Arul M.}",

note = "Publisher Copyright: {\textcopyright} 2015 Elsevier Inc.",

year = "2015",

month = may,

day = "30",

doi = "10.1016/j.cell.2015.05.001",

language = "English (US)",

volume = "161",

pages = "1215--1228",

journal = "Cell",

issn = "0092-8674",

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TY - JOUR

T1 - Integrative clinical genomics of advanced prostate cancer

AU - Robinson, Dan

AU - Van Allen, Eliezer M.

AU - Wu, Yi Mi

AU - Schultz, Nikolaus

AU - Lonigro, Robert J.

AU - Mosquera, Juan Miguel

AU - Montgomery, Bruce

AU - Taplin, Mary Ellen

AU - Pritchard, Colin C.

AU - Attard, Gerhardt

AU - Beltran, Himisha

AU - Abida, Wassim

AU - Bradley, Robert K.

AU - Vinson, Jake

AU - Cao, Xuhong

AU - Vats, Pankaj

AU - Kunju, Lakshmi P.

AU - Hussain, Maha

AU - Feng, Felix Y.

AU - Tomlins, Scott A.

AU - Cooney, Kathleen A.

AU - Smith, David C.

AU - Brennan, Christine

AU - Siddiqui, Javed

AU - Mehra, Rohit

AU - Chen, Yu

AU - Rathkopf, Dana E.

AU - Morris, Michael J.

AU - Solomon, Stephen B.

AU - Durack, Jeremy C.

AU - Reuter, Victor E.

AU - Gopalan, Anuradha

AU - Gao, Jianjiong

AU - Loda, Massimo

AU - Lis, Rosina T.

AU - Bowden, Michaela

AU - Balk, Stephen P.

AU - Gaviola, Glenn

AU - Sougnez, Carrie

AU - Gupta, Manaswi

AU - Yu, Evan Y.

AU - Mostaghel, Elahe A.

AU - Cheng, Heather H.

AU - Mulcahy, Hyojeong

AU - True, Lawrence D.

AU - Plymate, Stephen R.

AU - Dvinge, Heidi

AU - Ferraldeschi, Roberta

AU - Flohr, Penny

AU - Miranda, Susana

AU - Zafeiriou, Zafeiris

AU - Tunariu, Nina

AU - Mateo, Joaquin

AU - Perez-Lopez, Raquel

AU - Demichelis, Francesca

AU - Robinson, Brian D.

AU - Schiffman, Marc

AU - Nanus, David M.

AU - Tagawa, Scott T.

AU - Sigaras, Alexandros

AU - Eng, Kenneth W.

AU - Elemento, Olivier

AU - Sboner, Andrea

AU - Heath, Elisabeth I.

AU - Scher, Howard I.

AU - Pienta, Kenneth J.

AU - Kantoff, Philip

AU - De Bono, Johann S.

AU - Rubin, Mark A.

AU - Nelson, Peter S.

AU - Garraway, Levi A.

AU - Sawyers, Charles L.

AU - Chinnaiyan, Arul M.

PY - 2015/5/30

Y1 - 2015/5/30

N2 - Toward development of a precision medicine framework for metastatic, castration-resistant prostate cancer (mCRPC), we established a multi-institutional clinical sequencing infrastructure to conduct prospective whole-exome and transcriptome sequencing of bone or soft tissue tumor biopsies from a cohort of 150 mCRPC affected individuals. Aberrations of AR, ETS genes, TP53, and PTEN were frequent (40%-60% of cases), with TP53 and AR alterations enriched in mCRPC compared to primary prostate cancer. We identified new genomic alterations in PIK3CA/B, R-spondin, BRAF/RAF1, APC, β-catenin, and ZBTB16/PLZF. Moreover, aberrations of BRCA2, BRCA1, and ATM were observed at substantially higher frequencies (19.3% overall) compared to those in primary prostate cancers. 89% of affected individuals harbored a clinically actionable aberration, including 62.7% with aberrations in AR, 65% in other cancer-related genes, and 8% with actionable pathogenic germline alterations. This cohort study provides clinically actionable information that could impact treatment decisions for these affected individuals.

AB - Toward development of a precision medicine framework for metastatic, castration-resistant prostate cancer (mCRPC), we established a multi-institutional clinical sequencing infrastructure to conduct prospective whole-exome and transcriptome sequencing of bone or soft tissue tumor biopsies from a cohort of 150 mCRPC affected individuals. Aberrations of AR, ETS genes, TP53, and PTEN were frequent (40%-60% of cases), with TP53 and AR alterations enriched in mCRPC compared to primary prostate cancer. We identified new genomic alterations in PIK3CA/B, R-spondin, BRAF/RAF1, APC, β-catenin, and ZBTB16/PLZF. Moreover, aberrations of BRCA2, BRCA1, and ATM were observed at substantially higher frequencies (19.3% overall) compared to those in primary prostate cancers. 89% of affected individuals harbored a clinically actionable aberration, including 62.7% with aberrations in AR, 65% in other cancer-related genes, and 8% with actionable pathogenic germline alterations. This cohort study provides clinically actionable information that could impact treatment decisions for these affected individuals.

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UR - http://www.scopus.com/inward/citedby.url?scp=84930225081&partnerID=8YFLogxK

U2 - 10.1016/j.cell.2015.05.001

DO - 10.1016/j.cell.2015.05.001

M3 - Article

C2 - 26000489

AN - SCOPUS:84930225081

SN - 0092-8674

VL - 161

SP - 1215

EP - 1228

JO - Cell

JF - Cell

IS - 5

ER -

Integrative clinical genomics of advanced prostate cancer

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