Tracking the clonal origin of lethal prostate cancer

被引：410

作者：

Haffner, Michael C. ^{[1
]}

Mosbruger, Timothy ^{[1
]}

Esopi, David M. ^{[1
]}

Fedor, Helen ^{[2
]}

Heaphy, Christopher M. ^{[2
]}

Walker, David A. ^{[1
]}

Adejola, Nkosi ^{[1
]}

Guerel, Meltem ^{[1
]}

Hicks, Jessica ^{[2
]}

Meeker, Alan K. ^{[1
,2
,3
]}

Halushka, Marc K. ^{[2
]}

Simons, Jonathan W. ^{[4
]}

Isaacs, William B. ^{[1
,2
,3
]}

De Marzo, Angelo M. ^{[1
,2
,3
]}

Nelson, William G. ^{[1
,2
,3
]}

Yegnasubramanian, Srinivasan ^{[1
,2
,3
]}

机构：

[1] Johns Hopkins Sch Med, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA

[2] Johns Hopkins Sch Med, Dept Pathol, Baltimore, MD USA

[3] Johns Hopkins Sch Med, Brady Urol Inst, Baltimore, MD USA

[4] Prostate Canc Fdn, Santa Monica, CA USA

来源：

JOURNAL OF CLINICAL INVESTIGATION | 2013年 / 123卷 / 11期

关键词：

EVOLUTION; HETEROGENEITY; METASTASIS; LESS;

D O I：

10.1172/JCI70354

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

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.

引用

页码：4918 / 4922

页数：5

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