PMID- 12781447
OWN - NLM
STAT- MEDLINE
DCOM- 20030627
LR  - 20190816
IS  - 0165-4608 (Print)
IS  - 0165-4608 (Linking)
VI  - 143
IP  - 2
DP  - 2003 Jun
TI  - Modified allelic replication in lymphocytes of patients with neurofibromatosis 
      type 1.
PG  - 133-9
AB  - Transcription activity of genes is related to their replication timing, 
      accordingly gene activation is coupled with a shift from late replication to 
      early replication and vice versa. The relationship between replication timing and 
      gene expression is best manifested by monoallelically expressed genes which show 
      an asynchronous pattern of allelic replication, with the active allele 
      replicating earlier than the inactive counterpart. Biallelically expressed genes, 
      which normally replicate highly synchronously, when present in lymphocytes 
      derived from patients with various types of malignancies or premalignancies, 
      replicate highly asynchronously, similar to monoallelically expressed genes. 
      Since neurofibromatosis-type 1 (NF1) patients are at an increased risk to develop 
      malignancies, we used the fluorescence in situ hybridization (FISH) replication 
      assay and evaluated the level of replication synchrony of three cancer-implicated 
      genes (RB1, AML1, and CMYC) in lymphocytes derived from patients with NF1 without 
      malignancy. Each gene, which normally displayed synchrony in allelic replication, 
      in the patients' cells displayed loss of synchrony. The loss of replication 
      synchrony, of each gene, in the patients' cells was achieved by an advanced 
      replication of a single allele, which replicated remarkably earlier than its 
      normal scheduled timing. In addition, the second allele showed slightly earlier 
      replication timing than that normal for the gene. Thus, it is assumed that the 
      NF1 condition is associated with activation of cancer-implicated genes that may 
      be the cause for increased risk of patients to develop malignancies. As loss of 
      synchrony in allelic replication timing differentiates well between NF1 patients 
      and control subjects, this marker may have a potential use for identification of 
      presymptomatic carriers of NF1 disorders.
FAU - Reish, Orit
AU  - Reish O
AD  - Genetic Institute, Assaf Harofeh Medical Center, Zerifin, Israel. 
      oreish@post.tau.ac.il
FAU - Orlovski, Ana
AU  - Orlovski A
FAU - Mashevitz, Maya
AU  - Mashevitz M
FAU - Sher, Carron
AU  - Sher C
FAU - Libman, Vitalia
AU  - Libman V
FAU - Rosenblat, Malka
AU  - Rosenblat M
FAU - Avivi, Lydia
AU  - Avivi L
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Cancer Genet Cytogenet
JT  - Cancer genetics and cytogenetics
JID - 7909240
RN  - 0 (DNA, Neoplasm)
RN  - 0 (Phytohemagglutinins)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - *Alleles
MH  - Child
MH  - Child, Preschool
MH  - DNA Replication/*genetics
MH  - DNA, Neoplasm/genetics
MH  - Female
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Lymphocytes/drug effects/*metabolism
MH  - Male
MH  - Middle Aged
MH  - Neurofibromatosis 1/*genetics
MH  - Phytohemagglutinins/pharmacology
EDAT- 2003/06/05 05:00
MHDA- 2003/06/28 05:00
CRDT- 2003/06/05 05:00
PHST- 2003/06/05 05:00 [pubmed]
PHST- 2003/06/28 05:00 [medline]
PHST- 2003/06/05 05:00 [entrez]
AID - S0165460802008580 [pii]
AID - 10.1016/s0165-4608(02)00858-0 [doi]
PST - ppublish
SO  - Cancer Genet Cytogenet. 2003 Jun;143(2):133-9. doi: 
      10.1016/s0165-4608(02)00858-0.