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Copy number analysis indicates monoclonal origin of lethal metastatic prostate cancer.

Liu, Wennuan; Laitinen, Sari; Khan, Sofia; Vihinen, Mauno LU ; Kowalski, Jeanne; Yu, Guoqiang; Chen, Li; Ewing, Charles M; Eisenberger, Mario A and Carducci, Michael A, et al. (2009) In Nature Medicine 15(5). p.559-565
Abstract
Many studies have shown that primary prostate cancers are multifocal and are composed of multiple genetically distinct cancer cell clones. Whether or not multiclonal primary prostate cancers typically give rise to multiclonal or monoclonal prostate cancer metastases is largely unknown, although studies at single chromosomal loci are consistent with the latter case. Here we show through a high-resolution genome-wide single nucleotide polymorphism and copy number survey that most, if not all, metastatic prostate cancers have monoclonal origins and maintain a unique signature copy number pattern of the parent cancer cell while also accumulating a variable number of separate subclonally sustained changes. We find no relationship between... (More)
Many studies have shown that primary prostate cancers are multifocal and are composed of multiple genetically distinct cancer cell clones. Whether or not multiclonal primary prostate cancers typically give rise to multiclonal or monoclonal prostate cancer metastases is largely unknown, although studies at single chromosomal loci are consistent with the latter case. Here we show through a high-resolution genome-wide single nucleotide polymorphism and copy number survey that most, if not all, metastatic prostate cancers have monoclonal origins and maintain a unique signature copy number pattern of the parent cancer cell while also accumulating a variable number of separate subclonally sustained changes. We find no relationship between anatomic site of metastasis and genomic copy number change pattern. Taken together with past animal and cytogenetic studies of metastasis and recent single-locus genetic data in prostate and other metastatic cancers, these data indicate that despite common genomic heterogeneity in primary cancers, most metastatic cancers arise from a single precursor cancer cell. This study establishes that genomic archeology of multiple anatomically separate metastatic cancers in individuals can be used to define the salient genomic features of a parent cancer clone of proven lethal metastatic phenotype. (Less)
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keywords
DNA, Continental Population Groups: genetics, Pair 6: genetics, African Continental Ancestry Group: genetics, Pair 13: genetics, Human, Chromosomes, Neoplasm: genetics, Neoplasm Metastasis: genetics, Prostatic Neoplasms: genetics, Prostatic Neoplasms: mortality, Prostatic Neoplasms: pathology
in
Nature Medicine
volume
15
issue
5
pages
559 - 565
publisher
Nature Publishing Group
external identifiers
  • PMID:19363497
  • Scopus:67349257845
ISSN
1546-170X
DOI
10.1038/nm.1944
language
English
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no
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a5d939d3-84c9-46b5-9142-1cd6025588af (old id 3634796)
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http://www.ncbi.nlm.nih.gov/pubmed/19363497?dopt=Abstract
date added to LUP
2013-06-12 20:37:12
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2017-01-29 04:19:11
@article{a5d939d3-84c9-46b5-9142-1cd6025588af,
  abstract     = {Many studies have shown that primary prostate cancers are multifocal and are composed of multiple genetically distinct cancer cell clones. Whether or not multiclonal primary prostate cancers typically give rise to multiclonal or monoclonal prostate cancer metastases is largely unknown, although studies at single chromosomal loci are consistent with the latter case. Here we show through a high-resolution genome-wide single nucleotide polymorphism and copy number survey that most, if not all, metastatic prostate cancers have monoclonal origins and maintain a unique signature copy number pattern of the parent cancer cell while also accumulating a variable number of separate subclonally sustained changes. We find no relationship between anatomic site of metastasis and genomic copy number change pattern. Taken together with past animal and cytogenetic studies of metastasis and recent single-locus genetic data in prostate and other metastatic cancers, these data indicate that despite common genomic heterogeneity in primary cancers, most metastatic cancers arise from a single precursor cancer cell. This study establishes that genomic archeology of multiple anatomically separate metastatic cancers in individuals can be used to define the salient genomic features of a parent cancer clone of proven lethal metastatic phenotype.},
  author       = {Liu, Wennuan and Laitinen, Sari and Khan, Sofia and Vihinen, Mauno and Kowalski, Jeanne and Yu, Guoqiang and Chen, Li and Ewing, Charles M and Eisenberger, Mario A and Carducci, Michael A and Nelson, William G and Yegnasubramanian, Srinivasan and Luo, Jun and Wang, Yue and Xu, Jianfeng and Isaacs, William B and Visakorpi, Tapio and Bova, G Steven},
  issn         = {1546-170X},
  keyword      = {DNA,Continental Population Groups: genetics,Pair 6: genetics,African Continental Ancestry Group: genetics,Pair 13: genetics,Human,Chromosomes,Neoplasm: genetics,Neoplasm Metastasis: genetics,Prostatic Neoplasms: genetics,Prostatic Neoplasms: mortality,Prostatic Neoplasms: pathology},
  language     = {eng},
  number       = {5},
  pages        = {559--565},
  publisher    = {Nature Publishing Group},
  series       = {Nature Medicine},
  title        = {Copy number analysis indicates monoclonal origin of lethal metastatic prostate cancer.},
  url          = {http://dx.doi.org/10.1038/nm.1944},
  volume       = {15},
  year         = {2009},
}