Integrative Pan-Cancer Genomic and Transcriptomic Analyses of Refractory Metastatic Cancer

Yoann Pradat; Julien Viot; Andrey A. Yurchenko; Konstantin Gunbin; Luigi Cerbone; Marc Deloger; Guillaume Grisay; Loic Verlingue; Véronique Scott; Ismael Padioleau; Leonardo Panunzi; Stefan Michiels; Antoine Hollebecque; Gérôme Jules-Clément; Laura Mezquita; Antoine Lainé; Yohann Loriot; Benjamin Besse; Luc Friboulet; Fabrice André; Paul Henry Cournède; Daniel Gautheret; Sergey Ia Nikolaev

doi:10.1158/2159-8290.CD-22-0966

Integrative Pan-Cancer Genomic and Transcriptomic Analyses of Refractory Metastatic Cancer

Yoann Pradat, Julien Viot, Andrey A. Yurchenko, Konstantin Gunbin, Luigi Cerbone, Marc Deloger, Guillaume Grisay, Loic Verlingue, Véronique Scott, Ismael Padioleau, Leonardo Panunzi, Stefan Michiels, Antoine Hollebecque, Gérôme Jules-Clément, Laura Mezquita, Antoine Lainé, Yohann Loriot, Benjamin Besse, Luc Friboulet, Fabrice AndréPaul Henry Cournède, Daniel Gautheret, Sergey Ia Nikolaev

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15 Citations (Scopus)

Abstract

Metastatic relapse after treatment is the leading cause of cancer mortality, and known resistance mechanisms are missing for most treatments administered to patients. To bridge this gap, we analyze a pan-cancer cohort (META-PRISM) of 1,031 refractory metastatic tumors profiled via whole-exome and transcriptome sequencing. META-PRISM tumors, particularly prostate, bladder, and pancreatic types, displayed the most transformed genomes compared with primary untreated tumors. Standard-of-care resistance biomarkers were identified only in lung and colon cancers—9.6% of META-PRISM tumors, indicating that too few resistance mechanisms have received clinical validation. In contrast, we verified the enrichment of multiple investigational and hypothetical resistance mechanisms in treated compared with nontreated patients, thereby confirming their putative role in treatment resistance. Additionally, we demonstrated that molecular markers improve 6-month survival prediction, particularly in patients with advanced breast cancer. Our analysis establishes the utility of the META-PRISM cohort for investigating resistance mechanisms and performing predictive analyses in cancer.

Original language	English
Pages (from-to)	1116-1143
Number of pages	28
Journal	Cancer Discovery
Volume	13
Issue number	5
DOIs	https://doi.org/10.1158/2159-8290.CD-22-0966
Publication status	Published - 1 May 2023

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Pradat, Y., Viot, J., Yurchenko, A. A., Gunbin, K., Cerbone, L., Deloger, M., Grisay, G., Verlingue, L., Scott, V., Padioleau, I., Panunzi, L., Michiels, S., Hollebecque, A., Jules-Clément, G., Mezquita, L., Lainé, A., Loriot, Y., Besse, B., Friboulet, L., ... Nikolaev, S. I. (2023). Integrative Pan-Cancer Genomic and Transcriptomic Analyses of Refractory Metastatic Cancer. Cancer Discovery, 13(5), 1116-1143. https://doi.org/10.1158/2159-8290.CD-22-0966

@article{81f935a0bafa4abd9a51a9769c53714c,

title = "Integrative Pan-Cancer Genomic and Transcriptomic Analyses of Refractory Metastatic Cancer",

abstract = "Metastatic relapse after treatment is the leading cause of cancer mortality, and known resistance mechanisms are missing for most treatments administered to patients. To bridge this gap, we analyze a pan-cancer cohort (META-PRISM) of 1,031 refractory metastatic tumors profiled via whole-exome and transcriptome sequencing. META-PRISM tumors, particularly prostate, bladder, and pancreatic types, displayed the most transformed genomes compared with primary untreated tumors. Standard-of-care resistance biomarkers were identified only in lung and colon cancers—9.6% of META-PRISM tumors, indicating that too few resistance mechanisms have received clinical validation. In contrast, we verified the enrichment of multiple investigational and hypothetical resistance mechanisms in treated compared with nontreated patients, thereby confirming their putative role in treatment resistance. Additionally, we demonstrated that molecular markers improve 6-month survival prediction, particularly in patients with advanced breast cancer. Our analysis establishes the utility of the META-PRISM cohort for investigating resistance mechanisms and performing predictive analyses in cancer.",

author = "Yoann Pradat and Julien Viot and Yurchenko, {Andrey A.} and Konstantin Gunbin and Luigi Cerbone and Marc Deloger and Guillaume Grisay and Loic Verlingue and V{\'e}ronique Scott and Ismael Padioleau and Leonardo Panunzi and Stefan Michiels and Antoine Hollebecque and G{\'e}r{\^o}me Jules-Cl{\'e}ment and Laura Mezquita and Antoine Lain{\'e} and Yohann Loriot and Benjamin Besse and Luc Friboulet and Fabrice Andr{\'e} and Courn{\`e}de, {Paul Henry} and Daniel Gautheret and Nikolaev, {Sergey Ia}",

year = "2023",

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doi = "10.1158/2159-8290.CD-22-0966",

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Pradat, Y, Viot, J, Yurchenko, AA, Gunbin, K, Cerbone, L, Deloger, M, Grisay, G, Verlingue, L, Scott, V, Padioleau, I, Panunzi, L, Michiels, S, Hollebecque, A, Jules-Clément, G, Mezquita, L, Lainé, A, Loriot, Y, Besse, B, Friboulet, L, André, F, Cournède, PH, Gautheret, D & Nikolaev, SI 2023, 'Integrative Pan-Cancer Genomic and Transcriptomic Analyses of Refractory Metastatic Cancer', Cancer Discovery, vol. 13, no. 5, pp. 1116-1143. https://doi.org/10.1158/2159-8290.CD-22-0966

TY - JOUR

T1 - Integrative Pan-Cancer Genomic and Transcriptomic Analyses of Refractory Metastatic Cancer

AU - Pradat, Yoann

AU - Viot, Julien

AU - Yurchenko, Andrey A.

AU - Gunbin, Konstantin

AU - Cerbone, Luigi

AU - Deloger, Marc

AU - Grisay, Guillaume

AU - Verlingue, Loic

AU - Scott, Véronique

AU - Padioleau, Ismael

AU - Panunzi, Leonardo

AU - Michiels, Stefan

AU - Hollebecque, Antoine

AU - Jules-Clément, Gérôme

AU - Mezquita, Laura

AU - Lainé, Antoine

AU - Loriot, Yohann

AU - Besse, Benjamin

AU - Friboulet, Luc

AU - André, Fabrice

AU - Cournède, Paul Henry

AU - Gautheret, Daniel

AU - Nikolaev, Sergey Ia

PY - 2023/5/1

Y1 - 2023/5/1

N2 - Metastatic relapse after treatment is the leading cause of cancer mortality, and known resistance mechanisms are missing for most treatments administered to patients. To bridge this gap, we analyze a pan-cancer cohort (META-PRISM) of 1,031 refractory metastatic tumors profiled via whole-exome and transcriptome sequencing. META-PRISM tumors, particularly prostate, bladder, and pancreatic types, displayed the most transformed genomes compared with primary untreated tumors. Standard-of-care resistance biomarkers were identified only in lung and colon cancers—9.6% of META-PRISM tumors, indicating that too few resistance mechanisms have received clinical validation. In contrast, we verified the enrichment of multiple investigational and hypothetical resistance mechanisms in treated compared with nontreated patients, thereby confirming their putative role in treatment resistance. Additionally, we demonstrated that molecular markers improve 6-month survival prediction, particularly in patients with advanced breast cancer. Our analysis establishes the utility of the META-PRISM cohort for investigating resistance mechanisms and performing predictive analyses in cancer.

AB - Metastatic relapse after treatment is the leading cause of cancer mortality, and known resistance mechanisms are missing for most treatments administered to patients. To bridge this gap, we analyze a pan-cancer cohort (META-PRISM) of 1,031 refractory metastatic tumors profiled via whole-exome and transcriptome sequencing. META-PRISM tumors, particularly prostate, bladder, and pancreatic types, displayed the most transformed genomes compared with primary untreated tumors. Standard-of-care resistance biomarkers were identified only in lung and colon cancers—9.6% of META-PRISM tumors, indicating that too few resistance mechanisms have received clinical validation. In contrast, we verified the enrichment of multiple investigational and hypothetical resistance mechanisms in treated compared with nontreated patients, thereby confirming their putative role in treatment resistance. Additionally, we demonstrated that molecular markers improve 6-month survival prediction, particularly in patients with advanced breast cancer. Our analysis establishes the utility of the META-PRISM cohort for investigating resistance mechanisms and performing predictive analyses in cancer.

UR - http://www.scopus.com/inward/record.url?scp=85152372572&partnerID=8YFLogxK

U2 - 10.1158/2159-8290.CD-22-0966

DO - 10.1158/2159-8290.CD-22-0966

M3 - Article

C2 - 36862804

AN - SCOPUS:85152372572

SN - 2159-8274

VL - 13

SP - 1116

EP - 1143

JO - Cancer Discovery

JF - Cancer Discovery

IS - 5

ER -

Integrative Pan-Cancer Genomic and Transcriptomic Analyses of Refractory Metastatic Cancer

Abstract

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