Comprehensive assessment of DNA copy number alterations in human prostate cancers using Affymetrix 100K SNP mapping array

Wennuan Liu, Baoli Chang, Jurga Sauvageot, Latchezar Dimitrov, Marta Gielzak, Tao Li, Guifang Yan, Jishan Sun, Jielin Sun, Tamara S. Adams, Aubrey R. Turner, Jin Woo Kim, Deborah A. Meyers, Siqun Lilly Zheng, William B Isaacs, Jianfeng Xu

Research output: Contribution to journalArticle

Abstract

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 ≥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.

Original languageEnglish (US)
Pages (from-to)1018-1032
Number of pages15
JournalGenes Chromosomes and Cancer
Volume45
Issue number11
DOIs
StatePublished - Nov 2006

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ASJC Scopus subject areas

  • Cancer Research
  • Genetics

Cite this

Liu, W., Chang, B., Sauvageot, J., Dimitrov, L., Gielzak, M., Li, T., Yan, G., Sun, J., Sun, J., Adams, T. S., Turner, A. R., Kim, J. W., Meyers, D. A., Zheng, S. L., Isaacs, W. B., & Xu, J. (2006). Comprehensive assessment of DNA copy number alterations in human prostate cancers using Affymetrix 100K SNP mapping array. Genes Chromosomes and Cancer, 45(11), 1018-1032. https://doi.org/10.1002/gcc.20369