Tracking the clonal origin of lethal prostate cancer

Michael C. Haffner, Timothy Mosbruger, David M. Esopi, Helen Fedor, Christopher M Heaphy, David A. Walker, Nkosi Adejola, Meltem Gürel, Jessica Hicks, Alan Keith Meeker, Marc K Halushka, Jonathan W. Simons, William B Isaacs, Angelo Michael Demarzo, William G Nelson, S Yegnasubramanian

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)4918-4922
Number of pages5
JournalJournal of Clinical Investigation
Volume123
Issue number11
DOIs
StatePublished - Nov 1 2013

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Prostatic Neoplasms
Clone Cells
Neoplasms
Neoplasm Metastasis
Tumor Suppressor Proteins
Precision Medicine
Prostatectomy
Disease Progression
Lymph Nodes
Genome

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Tracking the clonal origin of lethal prostate cancer. / Haffner, Michael C.; Mosbruger, Timothy; Esopi, David M.; Fedor, Helen; Heaphy, Christopher M; Walker, David A.; Adejola, Nkosi; Gürel, Meltem; Hicks, Jessica; Meeker, Alan Keith; Halushka, Marc K; Simons, Jonathan W.; Isaacs, William B; Demarzo, Angelo Michael; Nelson, William G; Yegnasubramanian, S.

In: Journal of Clinical Investigation, Vol. 123, No. 11, 01.11.2013, p. 4918-4922.

Research output: Contribution to journalArticle

Haffner, MC, Mosbruger, T, Esopi, DM, Fedor, H, Heaphy, CM, Walker, DA, Adejola, N, Gürel, M, Hicks, J, Meeker, AK, Halushka, MK, Simons, JW, Isaacs, WB, Demarzo, AM, Nelson, WG & Yegnasubramanian, S 2013, 'Tracking the clonal origin of lethal prostate cancer', Journal of Clinical Investigation, vol. 123, no. 11, pp. 4918-4922. https://doi.org/10.1172/JCI70354
Haffner MC, Mosbruger T, Esopi DM, Fedor H, Heaphy CM, Walker DA et al. Tracking the clonal origin of lethal prostate cancer. Journal of Clinical Investigation. 2013 Nov 1;123(11):4918-4922. https://doi.org/10.1172/JCI70354
Haffner, Michael C. ; Mosbruger, Timothy ; Esopi, David M. ; Fedor, Helen ; Heaphy, Christopher M ; Walker, David A. ; Adejola, Nkosi ; Gürel, Meltem ; Hicks, Jessica ; Meeker, Alan Keith ; Halushka, Marc K ; Simons, Jonathan W. ; Isaacs, William B ; Demarzo, Angelo Michael ; Nelson, William G ; Yegnasubramanian, S. / Tracking the clonal origin of lethal prostate cancer. In: Journal of Clinical Investigation. 2013 ; Vol. 123, No. 11. pp. 4918-4922.
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