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

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

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 languageEnglish (US)
JournalJCO Precision Oncology
Volume3
DOIs
StatePublished - 2019
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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