Integrative Clinical Genomics of Advanced Prostate Cancer

@article{Robinson2015IntegrativeCG,
  title={Integrative Clinical Genomics of Advanced Prostate Cancer},
  author={Dan R. Robinson and Eliezer M. Van Allen and Yi-Mi Wu and Nikolaus D. Schultz and Robert J. Lonigro and Juan Miguel Mosquera and Bruce Montgomery and Mary-Ellen Taplin and Colin C. Pritchard and Gerhardt Attard and Himisha Beltran and Wassim Abida and Robert K. Bradley and Jake Vinson and Xuhong Cao and Pankaj Vats and Lakshmi Priya Kunju and Maha H.A. Hussain and Felix Y. Feng and Scott A. Tomlins and Kathleen A Cooney and David C. Smith and Christine A Brennan and Javed Siddiqui and Rohit Mehra and Yu Chen and Dana E. Rathkopf and Michael J. Morris and Stephen B. Solomon and Jeremy C. Durack and Victor E. Reuter and Anuradha Gopalan and Jianjiong Gao and Massimo Loda and Rosina T. Lis and Michaela Bowden and Steven P. Balk and Glenn C. Gaviola and Carrie Sougnez and Manaswi Gupta and Evan Y. Yu and Elahe A. Mostaghel and Heather H. Cheng and Hyojeong Mulcahy and Lawrence D. True and Stephen R. Plymate 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 Brian D. Robinson and Marc H. Schiffman and David M. Nanus and Scott T. Tagawa and Alexandros Sigaras and Kenneth Eng and Olivier Elemento and Andrea Sboner and Elisabeth I. Heath and Howard I. Scher and Kenneth J. Pienta and Philip W. Kantoff and Johann S. de Bono and Mark A. Rubin and Peter S. Nelson and Levi A. Garraway and Charles L. Sawyers and Arul M. Chinnaiyan},
  journal={Cell},
  year={2015},
  volume={161},
  pages={1215-1228}
}

Figures from this paper

Triple Aberrant Prostate Cancer (TAPC) - Aggregate role of aberrations in TP53, PTEN and RB1 on ETS gene fusions and prognosis in metastatic castrate resistant prostate cancer.
TLDR
This study identified a unique molecular signature consisting of combined aberrations in TP53, PTEN and RB1 that is associated with poorer overall survival, as well as increasing prevalence of ETS gene fusions and differential gene expression patterns favoring aggressive disease and tumor progression.
Molecular landscape of prostate cancer: implications for current clinical trials.
Prospective Genomic Profiling of Prostate Cancer Across Disease States Reveals Germline and Somatic Alterations That May Affect Clinical Decision Making.
TLDR
The findings support the routine use of tumor and germline DNA profiling for patients with advanced prostate cancer, for the purpose of guiding enrollment in targeted clinical trials and counseling families at increased risk of malignancy.
Genomic Profiling of Prostate Cancer: An Updated Review
TLDR
Emerging evidence for genomic profiling of prostate cancer is reviewed, especially focusing on associations between genomic alteration and clinical outcome, liquid biopsy, and actionable molecular alterations.
An Emerging Landscape for Canonical and Actionable Molecular Alterations in Primary and Metastatic Prostate Cancer
TLDR
Results lend support that genomic profiling for advanced prostate cancer may identify actionable targets not routinely used in the current metastatic paradigm, and clinically significant subgroups of patients demonstrating defects in DNA-repair pathways, intrinsic prostate cancer signaling pathways that may prevent antitumor immunity.
Targeted Next-Generation Sequencing in Men with Metastatic Prostate Cancer: a Pilot Study
TLDR
In this cohort, the use of tNGS was feasible, detected frequent genomic alterations, and was used late in the disease course, and further studies and larger portfolios of targeted therapy trials are needed to maximize the benefit of t NGS in this population.
Clinical implications of genetic aberrations in metastatic prostate cancer.
TLDR
Genomic aberrations in clinically relevant pathways in metastatic castration-resistant prostate cancer (mCRPC) are described for which therapeutic targeting is possible and genetic testing for mismatch repair deficiency is a standard of care.
Sequencing of prostate cancers identifies new cancer genes, routes of progression and drug targets
TLDR
Joint analysis of new and previously published sequencing data for primary and metastatic prostate cancers identifies new candidate driver mutations and provides insights into disease progression and potential drug targets.
Prospective Comprehensive Genomic Profiling of Primary and Metastatic Prostate Tumors
TLDR
Routine clinical CGP in the real-world setting identified GAs that are investigational biomarkers for targeted therapies in 57% of cases and could further inform selection of poly (ADP-ribose) polymerase inhibitors and immunotherapies, respectively.
...
...

References

SHOWING 1-10 OF 79 REFERENCES
The Mutational Landscape of Lethal Castrate Resistant Prostate Cancer
TLDR
The mutational landscape of a heavily treated metastatic cancer is described, novel mechanisms of AR signalling deregulated in prostate cancer are identified, and candidates for future study are prioritize.
Personalized Oncology Through Integrative High-Throughput Sequencing: A Pilot Study
TLDR
The mutations present in advanced cancers can be identified by integrative high-throughput sequencing to enable biomarker-driven clinical trials and, ultimately, treatment and the authors tested this approach by extensively characterizing cancers in several patients and then convening a Sequencing Tumor Board of experts to determine the appropriate treatment.
Characterization of KRAS rearrangements in metastatic prostate cancer.
TLDR
This is the first description of an oncogenic gene fusion of KRAS, one of the most studied proto-oncogenes, and emphasizing the importance of RAS-RAF-MAPK signaling in this disease.
The genomic complexity of primary human prostate cancer
TLDR
Genomic rearrangements may arise from transcriptional or chromatin aberrancies and engage prostate tumorigenic mechanisms, suggesting a link between chromatin or transcriptional regulation and the genesis of genomic aberrations.
Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer
TLDR
SPOP mutations may define a new molecular subtype of prostate cancer, with mutations involving the SPOP substrate-binding cleft in 6–15% of tumors across multiple independent cohorts.
Organoid Cultures Derived from Patients with Advanced Prostate Cancer
Successful whole-exome sequencing from a prostate cancer bone metastasis biopsy
TLDR
The feasibility of diagnostic bone metastases profiling and analysis that will be required for the widespread application of prospective ‘precision medicine’ to men with advanced PCa are demonstrated.
...
...