PMID- 15185343 OWN - NLM STAT- MEDLINE DCOM- 20040720 LR - 20160303 IS - 0020-7136 (Print) IS - 0020-7136 (Linking) VI - 111 IP - 1 DP - 2004 Aug 10 TI - Altered mode of allelic replication accompanied by aneuploidy in peripheral blood lymphocytes of prostate cancer patients. PG - 60-6 AB - Replication timing of the genetic material is a highly programmed process correlated with expression, stability and methylation capacity. An important aspect of that timing is the temporal order of allelic replication: a synchronous mode for biallelically expressed genes and an asynchronous for monoallelically expressed genes. Previous studies showed that malignancy is associated with changes in the inherent mode of allelic replication, and even normal cells of cancer patients display alterations in the replication of various genes. Using fluorescence in situ hybridization (FISH), we checked whether allelic-replication mode differentiates cancer patients from healthy individuals. We focused on prostate cancer (CAP), the most common diagnosed cancer and the second leading cause of cancer death in men over 50 years old. Five nonrelated genes and a nontranscribed DNA sequence associated with chromosomal segregation were used in our study. All 6 tested loci displayed in peripheral blood lymphocytes stimulated with phytohemagglutinin (PHA) of CAP patients loss of their inherent temporal order of allelic replication, coupled with aneuploidy, the outcome of chromosome malsegregation. The replication-timing modification is a reversible epigenetic alteration, evidenced by our ability to resurrect the normal pattern in all 6 tested loci by introducing an inhibitor of methyl transferase. On the other hand, the methylation-blocking agent failed to obliterate aneuploidy. The replication alteration accompanied by aneuploidy, detected in peripheral blood cells, distinguishes between CAP patients and individuals with benign prostate hyperplasia (BPH; a common disorder in elderly men) better than the routinely used blood marker, the prostate-specific antigen (PSA). CI - Copyright 2004 Wiley-Liss, Inc. FAU - Dotan, Zohar A AU - Dotan ZA AD - Department of Human Genetics and Molecular Medicine, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. FAU - Dotan, Aviva AU - Dotan A FAU - Ramon, Jacob AU - Ramon J FAU - Avivi, Lydia AU - Avivi L LA - eng PT - Journal Article PL - United States TA - Int J Cancer JT - International journal of cancer JID - 0042124 SB - IM MH - Aged MH - Aged, 80 and over MH - Alleles MH - *Aneuploidy MH - Cell Cycle MH - *DNA Replication MH - *Gene Expression Regulation, Neoplastic MH - Humans MH - *Lymphocytes MH - Male MH - Middle Aged MH - Prostatic Hyperplasia/genetics/physiopathology MH - Prostatic Neoplasms/*genetics/pathology MH - Time Factors EDAT- 2004/06/09 05:00 MHDA- 2004/07/21 05:00 CRDT- 2004/06/09 05:00 PHST- 2004/06/09 05:00 [pubmed] PHST- 2004/07/21 05:00 [medline] PHST- 2004/06/09 05:00 [entrez] AID - 10.1002/ijc.20237 [doi] PST - ppublish SO - Int J Cancer. 2004 Aug 10;111(1):60-6. doi: 10.1002/ijc.20237.