Tracking the clonal origin of lethal prostate cancer.
Michael C. Haffner,Timothy Mosbruger,David M. Esopi,Helen Fedor,Christopher M. Heaphy,David Walker,Nkosi Adejola,Meltem Gürel,Jessica Hicks,Alan K. Meeker,Marc K. Halushka,Jonathan W. Simons,William B. Isaacs,Angelo M. De Marzo,William G. Nelson,Srinivasan Yegnasubramanian +15 more
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TLDR
This case illustrates the potential need in precision medicine to longitudinally sample metastatic lesions to capture the evolving constellation of alterations during progression and highlights the potential importance of developing and implementing molecular prognostic and predictive markers to augment current pathological evaluation and delineate clonal heterogeneity.Abstract:
Recent controversies surrounding prostate cancer overtreatment emphasize the critical need to delineate the molecular features associated with progression to lethal metastatic disease. Here, we have used whole-genome sequencing and molecular pathological analyses to characterize the lethal cell clone in a patient who died of prostate cancer. We tracked the evolution of the lethal cell clone from the primary cancer to metastases through samples collected during disease progression and at the time of death. Surprisingly, these analyses revealed that the lethal clone arose from a small, relatively low-grade cancer focus in the primary tumor, and not from the bulk, higher-grade primary cancer or from a lymph node metastasis resected at prostatectomy. Despite being limited to one case, these findings highlight the potential importance of developing and implementing molecular prognostic and predictive markers, such as alterations of tumor suppressor proteins PTEN or p53, to augment current pathological evaluation and delineate clonal heterogeneity. Furthermore, this case illustrates the potential need in precision medicine to longitudinally sample metastatic lesions to capture the evolving constellation of alterations during progression. Similar comprehensive studies of additional prostate cancer cases are warranted to understand the extent to which these issues may challenge prostate cancer clinical management.read more
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SF-010-4 Distant metastasis occurs late during the genetic evolution of pancreatic cancer
TL;DR: A quantitative analysis of the timing of the genetic evolution of pancreatic cancer was performed, indicating at least a decade between the occurrence of the initiating mutation and the birth of the parental, non-metastatic founder cell.
Journal ArticleDOI
Emerging Biological Principles of Metastasis
TL;DR: The cellular and molecular mechanisms involved in metastasis are summarized, with a focus on carcinomas where the most is known, and the general principles of metastasis that have begun to emerge are highlighted.
Journal ArticleDOI
Biological and Therapeutic Impact of Intratumor Heterogeneity in Cancer Evolution
TL;DR: The processes shaping the cancer genome are explored, placing these within the context of tumor evolution and their impact on intratumor heterogeneity and drug development.
Journal ArticleDOI
Genomic Characterization of Brain Metastases Reveals Branched Evolution and Potential Therapeutic Targets
Priscilla K. Brastianos,Scott L. Carter,Scott L. Carter,Sandro Santagata,Sandro Santagata,Daniel P. Cahill,Amaro Taylor-Weiner,Robert T. Jones,Eliezer M. Van Allen,Eliezer M. Van Allen,Michael S. Lawrence,Peleg M. Horowitz,Kristian Cibulskis,Keith L. Ligon,Keith L. Ligon,Josep Tabernero,Joan Seoane,Elena Martínez-Sáez,William T. Curry,Ian F. Dunn,Sun Ha Paek,Sung Hye Park,Aaron McKenna,Aaron Chevalier,Mara Rosenberg,Fred G. Barker,Corey M. Gill,Paul Van Hummelen,Aaron R. Thorner,Bruce E. Johnson,Mai P. Hoang,Toni K. Choueiri,Sabina Signoretti,Carrie Sougnez,Michael S. Rabin,Nan Lin,Eric P. Winer,Anat Stemmer-Rachamimov,Matthew Meyerson,Levi A. Garraway,Levi A. Garraway,Stacey Gabriel,Eric S. Lander,Rameen Beroukhim,Rameen Beroukhim,Tracy T. Batchelor,José Baselga,David N. Louis,Gad Getz,Gad Getz,William C. Hahn,William C. Hahn +51 more
TL;DR: Stricker et al. as discussed by the authors performed whole-exome sequencing of 86 matched brain metastases, primary tumors, and normal tissue and found potentially clinically informative alterations in the brain metastasis not detected in the matched primary-tumor sample.
Journal Article
The Principles and Practice of Medicine
TL;DR: This work is one of the few large works which one would gladly have had even fuller; its whole contents are of such a quality that curtailment in any section would have been a loss.
References
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Cancer statistics, 2012
TL;DR: The reduction in overall cancer death rates since 1990 in men and 1991 in women translates to the avoidance of about 1,024,400 deaths from cancer, which can be accelerated by applying existing cancer control knowledge across all segments of the population, with an emphasis on those groups in the lowest socioeconomic bracket.
Journal ArticleDOI
Intratumor heterogeneity and branched evolution revealed by multiregion sequencing.
Marco Gerlinger,Andrew Rowan,Stuart Horswell,James Larkin,David Endesfelder,Eva Grönroos,Pierre Martinez,Nicholas Matthews,Aengus Stewart,Patrick S. Tarpey,Ignacio Varela,Benjamin Phillimore,Sharmin Begum,Neil Q. McDonald,Adam Butler,David T. Jones,Keiran Raine,Calli Latimer,Claudio R. Santos,Mahrokh Nohadani,Aron Charles Eklund,Bradley Spencer-Dene,Graham Clark,Lisa Pickering,Gordon Stamp,Martin Gore,Zoltan Szallasi,Zoltan Szallasi,Julian Downward,P. Andrew Futreal,Charles Swanton +30 more
TL;DR: Intratumor heterogeneity can lead to underestimation of the tumor genomics landscape portrayed from single tumor-biopsy samples and may present major challenges to personalized-medicine and biomarker development.
Journal ArticleDOI
The mutational landscape of lethal castration-resistant prostate cancer
Catherine S. Grasso,Yi-Mi Wu,Dan R. Robinson,Xuhong Cao,Saravana M. Dhanasekaran,Amjad Khan,Michael J. Quist,Xiaojun Jing,Robert J. Lonigro,J. Chad Brenner,Irfan A. Asangani,Bushra Ateeq,Sang Y. Chun,Javed Siddiqui,Lee Sam,Matt Anstett,Rohit Mehra,John R. Prensner,Nallasivam Palanisamy,Gregory A. Ryslik,Fabio Vandin,Benjamin J. Raphael,Lakshmi P. Kunju,Daniel R. Rhodes,Kenneth J. Pienta,Arul M. Chinnaiyan,Scott A. Tomlins +26 more
TL;DR: 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.
Journal ArticleDOI
Distant metastasis occurs late during the genetic evolution of pancreatic cancer
Shinichi Yachida,Siân Jones,Ivana Bozic,Tibor Antal,Tibor Antal,Rebecca J. Leary,Baojin Fu,Mihoko Kamiyama,Ralph H. Hruban,James R. Eshleman,Martin A. Nowak,Victor E. Velculescu,Kenneth W. Kinzler,Bert Vogelstein,Christine A. Iacobuzio-Donahue +14 more
TL;DR: In this article, the authors rely on data generated by sequencing the genomes of seven pancreatic cancer metastases to evaluate the clonal relationships among primary and metastatic cancers and find that clonal populations that give rise to distant metastases are represented within the primary carcinoma, but these clones are genetically evolved from the original parental, non-metastatic clone.
SF-010-4 Distant metastasis occurs late during the genetic evolution of pancreatic cancer
TL;DR: A quantitative analysis of the timing of the genetic evolution of pancreatic cancer was performed, indicating at least a decade between the occurrence of the initiating mutation and the birth of the parental, non-metastatic founder cell.
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