Copy Number Analysis Indicates Monoclonal Origin of Lethal Metastatic Prostate Cancer

By Wennuan Liu, Sari Laitinen, Sofia Khan, Mauno Vihinen, J. Kowalski, Guoqiang Yu, Li Chen, C. Ewing, M. Eisenberger, M. Carducci and 8 more. Nature Medicine, 2009

689 citations recorded by the source corpus.

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.

Subfields: Cancer Research, Pulmonary and Respiratory Medicine, Surgery

View Paper: https://www.semanticscholar.org/paper/b00414781d1feafcb444c484c35cd4f926a89cc7

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In Pulmonary and Respiratory Medicine

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Citations in the corpus

Genomic characterization of brain metastases reveals branched evolution and potential therapeutic targets (2015, background): “Because cancers are genetically heterogeneous (3-9), sampling a cancer in two different locations is expected to reveal mutations exclusive to each sample.”
EMERGING BIOLOGICAL PRINCIPLES OF METASTASIS (2017, neutral): “…that were resected synchronously, while others have compared metastases sampled up to 17 years after resection of the corresponding primary tumors; both have found genetic similarities between the two tissues (Campbell et al., 2010; Ding et al., 2010; Haffner et al., 2013; Liu et al., 2009).”
Androgen-induced TOP2B mediated double strand breaks and prostate cancer gene rearrangements (2010, background): “Examination of previously published datasets revealed that genomic breakpoints in TMPRSS2 and ERG occur most frequently at the ∼25-kb region between exon 1 and exon 4 of TMPRSS2 and at a ∼75-kb stretch in intron 3 of ERG”
Tumor heterogeneity: causes and consequences (2009, background): “CGH is one of the most widely used techniques in studies of intra-tumor clonal heterogeneity.”
Tumor Metastasis: Molecular Insights and Evolving Paradigms (2011, neutral): “Finally, genomic analyses of patient-matched primary prostate tumors and metastases revealed that the metastases bear the copy number signature of the primary tumor from which they were initially spawned (Liu et al., 2009).”
Absolute quantification of somatic DNA alterations in human cancer (2012, background): “The analysis of clonality presented in this work offers a path forward for clinical sequencing of cancer, and provides means to address recently reported concerns regarding intra-tumor heterogeneity 50, 14, 44, 15, 45, 51,52 .”
A Unique Metastasis Gene Signature Enables Prediction of Tumor Relapse in Early Stage Hepatocellular Carcinoma Patients (2010, neutral): “Similarly, copy number analysis of prostate cancers and their metastasis revealed that lethal metastatic prostate cancer is of monoclonal origin and that most metastatic cancers arise from a single cell (37).”
Molecular genetics of prostate cancer: new prospects for old challenges. (2010, background): “2004), molecular and cytogenetic analyses show that multiple metastases in the same patient are clonally related, indicating that advanced prostate cancer is monoclonal (Mehra et al. 2008; Liu et al. 2009).”