Comprehensive assessment of DNA copy number alterations in human prostate cancers using Affymetrix 100K SNP mapping array.
Although multiple recurrent chromosomal alterations have been identified in prostate cancer cells, the specific genes driving the apparent selection of these changes remain largely unknown. In part, this uncertainty is due to the limited resolution of the techniques used to detect these alterations. In this study, we applied a high-resolution genome-wide method, Affymetrix 100K SNP mapping array, to screen for somatic DNA copy number (CN) alterations among 22 pairs of samples from primary prostate cancers and matched nonmalignant tissues. We detected 355 recurrent deletions and 223 recurrent gains, many of which were novel. As expected, the sizes of novel alterations tend to be smaller. Importantly, among tumors with increasing grade, Gleason sum 6, 7, and 8, we found a significant trend of larger number of alterations in the tumors with higher grade. Overall, gains are significantly more likely to occur within genes (74%) than are deletions (49%). However, when we looked at the most frequent CN alterations, defined as those in > or =4 subjects, we observed that both gains (85%) and deletions (57%) occur preferentially within genes. An example of a novel, recurrent alteration observed in this study was a deletion between the ERG and TMPRSS2 genes on chromosome 21, presumably related to the recently identified fusion transcripts from these two genes. Results from this study provide a basis for a systematic and comprehensive cataloging of CN alterations associated with grades of prostate cancer, and the subsequent identification of specific genes that associated with initiation and progression of the disease. This article contains supplementary material available via the Internet at http://www.interscience.wiley.com/jpages/1045-2257/suppmat
Liu
Wennuan
W
Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
Chang
Baoli
B
Sauvageot
Jurga
J
Dimitrov
Latchezar
L
Gielzak
Marta
M
Li
Tao
T
Yan
Guifang
G
Sun
Jishan
J
Sun
Jielin
J
Adams
Tamara S
TS
Turner
Aubrey R
AR
Kim
Jin Woo
JW
Meyers
Deborah A
DA
Zheng
Siqun Lilly
SL
Isaacs
William B
WB
Xu
Jianfeng
J
D000368:Aged; D004273:DNA, Neoplasm / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D018628:Gene Dosage; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D011471:Prostatic Neoplasms / Q000235:genetics*; D012697:Serine Endopeptidases / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics; D000071230:Transcriptional Regulator ERG
D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; C072312:ERG protein, human; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; D012697:Serine Endopeptidases; C421305:TMPRSS2 protein, human