Integrative molecular analysis of patients with advanced and metastatic cancer

Verena Sailer; Kenneth Wa; Tuo Zhang; Rohan Bareja; David J. Pisapia; Alexandros Sigaras; Bhavneet Bhinder; Alessandro Romanel; David Wilkes; Evan Sticca; Joanna Cyrta; Rema Rao; Sheena Sahota; Chantal Pauli; Shaham Beg; Samaneh Motanagh; Myriam Kossai; Jacqueline Fontugne; Loredana Puca; Hanna Rennert; Jenny Zhaoying Xiang; Noah Greco; Rob Kim; Theresa Y. MacDonald; Terra McNary; Mirjam Blattner-Johnson; Marc H. Schiffman; Bishoy M. Faltas; Jeffrey P. Greenfield; David Rickman; Eleni Andreopoulou; Kevin Holcomb; Linda T. Vahdat; Douglas S. Scherr; Koen van Besien; Christopher E. Barbieri; Brian D. Robinson; Howard Alan Fine; Allyson J. Ocean; Ana Molina; Manish A. Shah; David M. Nanus; Qiulu Pan; Francesca Demichelis; Scott T. Tagawa; Wei Song; Juan Miguel Mosquera; Andrea Sboner; Mark A. Rubin; Olivier Elemento; Himisha Beltran

doi:10.1200/PO.19.00047

Integrative molecular analysis of patients with advanced and metastatic cancer

Verena Sailer, Kenneth Wa, Tuo Zhang, Rohan Bareja, David J. Pisapia, Alexandros Sigaras, Bhavneet Bhinder, Alessandro Romanel, David Wilkes, Evan Sticca, Joanna Cyrta, Rema Rao, Sheena Sahota, Chantal Pauli, Shaham Beg, Samaneh Motanagh, Myriam Kossai, Jacqueline Fontugne, Loredana Puca, Hanna RennertJenny Zhaoying Xiang, Noah Greco, Rob Kim, Theresa Y. MacDonald, Terra McNary, Mirjam Blattner-Johnson, Marc H. Schiffman, Bishoy M. Faltas, Jeffrey P. Greenfield, David Rickman, Eleni Andreopoulou, Kevin Holcomb, Linda T. Vahdat, Douglas S. Scherr, Koen van Besien, Christopher E. Barbieri, Brian D. Robinson, Howard Alan Fine, Allyson J. Ocean, Ana Molina, Manish A. Shah, David M. Nanus, Qiulu Pan, Francesca Demichelis, Scott T. Tagawa, Wei Song, Juan Miguel Mosquera, Andrea Sboner, Mark A. Rubin, Olivier Elemento, Himisha Beltran^*

^*Corresponding author for this work

Institute of Pathology

37 Citations (Scopus)

Abstract

PURPOSE We developed a precision medicine program for patients with advanced cancer using integrative whole-exome sequencing and transcriptome analysis. PATIENTS AND METHODS Five hundred fifteen patients with locally advanced/metastatic solid tumors were prospectively enrolled, and paired tumor/normal sequencing was performed. Seven hundred fifty-nine tumors from 515 patients were evaluated. RESULTS Most frequent tumor types were prostate (19.4%), brain (16.5%), bladder (15.4%), and kidney cancer (9.2%). Most frequently altered genes were TP53 (33%), CDKN2A (11%), APC (10%), KTM2D (8%), PTEN (8%), and BRCA2 (8%). Pathogenic germline alterations were present in 10.7% of patients, most frequently CHEK2 (1.9%), BRCA1 (1.5%), BRCA2 (1.5%), and MSH6 (1.4%). Novel gene fusions were identified, including a RBM47-CDK12 fusion in a metastatic prostate cancer sample. The rate of clinically relevant alterations was 39% by whole-exome sequencing, which was improved by 16% by adding RNA sequencing. In patients with more than one sequenced tumor sample (n = 146), 84.62% of actionable mutations were concordant. CONCLUSION Integrative analysis may uncover informative alterations for an advanced pan-cancer patient population. These alterations are consistent in spatially and temporally heterogeneous samples.

Original language	English
Journal	JCO Precision Oncology
Volume	3
Pages (from-to)	1-12
Number of pages	12
ISSN	2473-4284
DOIs	https://doi.org/10.1200/PO.19.00047
Publication status	Published - 2019

Funding

Supported by the Englander Institute for Precision Medicine of Weill Cornell Medicine and New York Presbyterian, the Translational Research Program of the Department of Pathology and Laboratory Medicine at Weill Cornell Medicine. Funded by Department of Defense Grants No. PC121341 (H.B.) and PC160264 (D.R., H.B.), the Prostate Cancer Foundation (L.P., M.A.R., and H.B.), and National Cancer Institute SPORE in Prostate Cancer Grant No. P50-CA211024 (J.M.M., M.A.R., O.E., and H.B.).

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Research Areas and Centers

Research Area: Luebeck Integrated Oncology Network (LION)
Centers: University Cancer Center Schleswig-Holstein (UCCSH)

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10.1200/PO.19.00047

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Sailer, V., Wa, K., Zhang, T., Bareja, R., Pisapia, D. J., Sigaras, A., Bhinder, B., Romanel, A., Wilkes, D., Sticca, E., Cyrta, J., Rao, R., Sahota, S., Pauli, C., Beg, S., Motanagh, S., Kossai, M., Fontugne, J., Puca, L., ... Beltran, H. (2019). Integrative molecular analysis of patients with advanced and metastatic cancer. JCO Precision Oncology, 3, 1-12. https://doi.org/10.1200/PO.19.00047

@article{eea19c1752fb48e59895d8b23948d11d,

title = "Integrative molecular analysis of patients with advanced and metastatic cancer",

abstract = "PURPOSE We developed a precision medicine program for patients with advanced cancer using integrative whole-exome sequencing and transcriptome analysis. PATIENTS AND METHODS Five hundred fifteen patients with locally advanced/metastatic solid tumors were prospectively enrolled, and paired tumor/normal sequencing was performed. Seven hundred fifty-nine tumors from 515 patients were evaluated. RESULTS Most frequent tumor types were prostate (19.4\%), brain (16.5\%), bladder (15.4\%), and kidney cancer (9.2\%). Most frequently altered genes were TP53 (33\%), CDKN2A (11\%), APC (10\%), KTM2D (8\%), PTEN (8\%), and BRCA2 (8\%). Pathogenic germline alterations were present in 10.7\% of patients, most frequently CHEK2 (1.9\%), BRCA1 (1.5\%), BRCA2 (1.5\%), and MSH6 (1.4\%). Novel gene fusions were identified, including a RBM47-CDK12 fusion in a metastatic prostate cancer sample. The rate of clinically relevant alterations was 39\% by whole-exome sequencing, which was improved by 16\% by adding RNA sequencing. In patients with more than one sequenced tumor sample (n = 146), 84.62\% of actionable mutations were concordant. CONCLUSION Integrative analysis may uncover informative alterations for an advanced pan-cancer patient population. These alterations are consistent in spatially and temporally heterogeneous samples.",

author = "Verena Sailer and Kenneth Wa and Tuo Zhang and Rohan Bareja and Pisapia, \{David J.\} and Alexandros Sigaras and Bhavneet Bhinder and Alessandro Romanel and David Wilkes and Evan Sticca and Joanna Cyrta and Rema Rao and Sheena Sahota and Chantal Pauli and Shaham Beg and Samaneh Motanagh and Myriam Kossai and Jacqueline Fontugne and Loredana Puca and Hanna Rennert and Xiang, \{Jenny Zhaoying\} and Noah Greco and Rob Kim and MacDonald, \{Theresa Y.\} and Terra McNary and Mirjam Blattner-Johnson and Schiffman, \{Marc H.\} and Faltas, \{Bishoy M.\} and Greenfield, \{Jeffrey P.\} and David Rickman and Eleni Andreopoulou and Kevin Holcomb and Vahdat, \{Linda T.\} and Scherr, \{Douglas S.\} and \{van Besien\}, Koen and Barbieri, \{Christopher E.\} and Robinson, \{Brian D.\} and \{Alan Fine\}, Howard and Ocean, \{Allyson J.\} and Ana Molina and Shah, \{Manish A.\} and Nanus, \{David M.\} and Qiulu Pan and Francesca Demichelis and Tagawa, \{Scott T.\} and Wei Song and Mosquera, \{Juan Miguel\} and Andrea Sboner and Rubin, \{Mark A.\} and Olivier Elemento and Himisha Beltran",

note = "Publisher Copyright: {\textcopyright} 2019 by American Society of Clinical Oncology",

year = "2019",

doi = "10.1200/PO.19.00047",

language = "English",

volume = "3",

pages = "1--12",

journal = "JCO Precision Oncology",

issn = "2473-4284",

}

Sailer, V, Wa, K, Zhang, T, Bareja, R, Pisapia, DJ, Sigaras, A, Bhinder, B, Romanel, A, Wilkes, D, Sticca, E, Cyrta, J, Rao, R, Sahota, S, Pauli, C, Beg, S, Motanagh, S, Kossai, M, Fontugne, J, Puca, L, Rennert, H, Xiang, JZ, Greco, N, Kim, R, MacDonald, TY, McNary, T, Blattner-Johnson, M, Schiffman, MH, Faltas, BM, Greenfield, JP, Rickman, D, Andreopoulou, E, Holcomb, K, Vahdat, LT, Scherr, DS, van Besien, K, Barbieri, CE, Robinson, BD, Alan Fine, H, Ocean, AJ, Molina, A, Shah, MA, Nanus, DM, Pan, Q, Demichelis, F, Tagawa, ST, Song, W, Mosquera, JM, Sboner, A, Rubin, MA, Elemento, O & Beltran, H 2019, 'Integrative molecular analysis of patients with advanced and metastatic cancer', JCO Precision Oncology, vol. 3, pp. 1-12. https://doi.org/10.1200/PO.19.00047

TY - JOUR

T1 - Integrative molecular analysis of patients with advanced and metastatic cancer

AU - Sailer, Verena

AU - Wa, Kenneth

AU - Zhang, Tuo

AU - Bareja, Rohan

AU - Pisapia, David J.

AU - Sigaras, Alexandros

AU - Bhinder, Bhavneet

AU - Romanel, Alessandro

AU - Wilkes, David

AU - Sticca, Evan

AU - Cyrta, Joanna

AU - Rao, Rema

AU - Sahota, Sheena

AU - Pauli, Chantal

AU - Beg, Shaham

AU - Motanagh, Samaneh

AU - Kossai, Myriam

AU - Fontugne, Jacqueline

AU - Puca, Loredana

AU - Rennert, Hanna

AU - Xiang, Jenny Zhaoying

AU - Greco, Noah

AU - Kim, Rob

AU - MacDonald, Theresa Y.

AU - McNary, Terra

AU - Blattner-Johnson, Mirjam

AU - Schiffman, Marc H.

AU - Faltas, Bishoy M.

AU - Greenfield, Jeffrey P.

AU - Rickman, David

AU - Andreopoulou, Eleni

AU - Holcomb, Kevin

AU - Vahdat, Linda T.

AU - Scherr, Douglas S.

AU - van Besien, Koen

AU - Barbieri, Christopher E.

AU - Robinson, Brian D.

AU - Alan Fine, Howard

AU - Ocean, Allyson J.

AU - Molina, Ana

AU - Shah, Manish A.

AU - Nanus, David M.

AU - Pan, Qiulu

AU - Demichelis, Francesca

AU - Tagawa, Scott T.

AU - Song, Wei

AU - Mosquera, Juan Miguel

AU - Sboner, Andrea

AU - Rubin, Mark A.

AU - Elemento, Olivier

AU - Beltran, Himisha

PY - 2019

Y1 - 2019

N2 - PURPOSE We developed a precision medicine program for patients with advanced cancer using integrative whole-exome sequencing and transcriptome analysis. PATIENTS AND METHODS Five hundred fifteen patients with locally advanced/metastatic solid tumors were prospectively enrolled, and paired tumor/normal sequencing was performed. Seven hundred fifty-nine tumors from 515 patients were evaluated. RESULTS Most frequent tumor types were prostate (19.4%), brain (16.5%), bladder (15.4%), and kidney cancer (9.2%). Most frequently altered genes were TP53 (33%), CDKN2A (11%), APC (10%), KTM2D (8%), PTEN (8%), and BRCA2 (8%). Pathogenic germline alterations were present in 10.7% of patients, most frequently CHEK2 (1.9%), BRCA1 (1.5%), BRCA2 (1.5%), and MSH6 (1.4%). Novel gene fusions were identified, including a RBM47-CDK12 fusion in a metastatic prostate cancer sample. The rate of clinically relevant alterations was 39% by whole-exome sequencing, which was improved by 16% by adding RNA sequencing. In patients with more than one sequenced tumor sample (n = 146), 84.62% of actionable mutations were concordant. CONCLUSION Integrative analysis may uncover informative alterations for an advanced pan-cancer patient population. These alterations are consistent in spatially and temporally heterogeneous samples.

AB - PURPOSE We developed a precision medicine program for patients with advanced cancer using integrative whole-exome sequencing and transcriptome analysis. PATIENTS AND METHODS Five hundred fifteen patients with locally advanced/metastatic solid tumors were prospectively enrolled, and paired tumor/normal sequencing was performed. Seven hundred fifty-nine tumors from 515 patients were evaluated. RESULTS Most frequent tumor types were prostate (19.4%), brain (16.5%), bladder (15.4%), and kidney cancer (9.2%). Most frequently altered genes were TP53 (33%), CDKN2A (11%), APC (10%), KTM2D (8%), PTEN (8%), and BRCA2 (8%). Pathogenic germline alterations were present in 10.7% of patients, most frequently CHEK2 (1.9%), BRCA1 (1.5%), BRCA2 (1.5%), and MSH6 (1.4%). Novel gene fusions were identified, including a RBM47-CDK12 fusion in a metastatic prostate cancer sample. The rate of clinically relevant alterations was 39% by whole-exome sequencing, which was improved by 16% by adding RNA sequencing. In patients with more than one sequenced tumor sample (n = 146), 84.62% of actionable mutations were concordant. CONCLUSION Integrative analysis may uncover informative alterations for an advanced pan-cancer patient population. These alterations are consistent in spatially and temporally heterogeneous samples.

UR - https://www.scopus.com/pages/publications/85080860385

U2 - 10.1200/PO.19.00047

DO - 10.1200/PO.19.00047

M3 - Journal articles

AN - SCOPUS:85080860385

SN - 2473-4284

VL - 3

SP - 1

EP - 12

JO - JCO Precision Oncology

JF - JCO Precision Oncology

ER -

Integrative molecular analysis of patients with advanced and metastatic cancer

Abstract

Funding

UN SDGs

Research Areas and Centers

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