Copy number analysis indicates monoclonal origin of lethal metastatic prostate cancer.
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.
Wennuan
W
Liu
Sari
S
Laitinen
Sofia
S
Khan
Mauno
M
Vihinen
Jeanne
J
Kowalski
Guoqiang
G
Yu
Li
L
Chen
Charles M
CM
Ewing
Mario A
MA
Eisenberger
Michael A
MA
Carducci
William G
WG
Nelson
Srinivasan
S
Yegnasubramanian
Jun
J
Luo
Yue
Y
Wang
Jianfeng
J
Xu
William B
WB
Isaacs
Tapio
T
Visakorpi
G Steven
GS
Bova
D000818:Animals; D044383:Black People / Q000235:genetics; D002874:Chromosome Mapping; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D055028:Comparative Genomic Hybridization; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000235:genetics; D006801:Humans; D008297:Male; D009362:Neoplasm Metastasis / Q000235:genetics; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D044469:Racial Groups / Q000235:genetics; D017384:Sequence Deletion
D004273:DNA, Neoplasm