PMID- 10679916
OWN - NLM
STAT- MEDLINE
DCOM- 20000309
LR  - 20061115
IS  - 1045-2257 (Print)
IS  - 1045-2257 (Linking)
VI  - 27
IP  - 3
DP  - 2000 Mar
TI  - Modification in the inherent mode of allelic replication in lymphocytes of 
      patients suffering from renal cell carcinoma: a novel genetic alteration 
      associated with malignancy.
PG  - 270-7
AB  - Using fluorescence in situ hybridization (FISH) to interphase nuclei, we examined 
      the replication timing of 1 allele relative to its counterpart in PHA-stimulated 
      peripheral blood lymphocytes of normal subjects and patients suffering from a 
      solid tumor (renal cell carcinoma). In the FISH assay, an unreplicated DNA 
      sequence is identified by a single dot-like hybridization signal, whereas a 
      replicated region gives rise to a duplicated, bipartite signal. Accordingly, 
      lymphocytes of normal individuals show 2 patterns of allelic replication: (i) 
      synchronized replication of allelic counterparts, as exemplified by the 
      biallelically expressed loci TP53 and D21S55; and (ii) non-synchronized 
      replication of allelic partners, as exemplified by the early and late replicating 
      alleles of GABRB3, an imprinted locus subjected to monoallelic expression. 
      However, when present in lymphocytes of the cancer patients, all 3 loci change 
      their replication mode: alleles of TP53 and D21S55 become asynchronous, whereas 
      the early replicating allele of GABRB3 delays replication, leading to relaxation 
      in the imprinted mode of replication. Based on the tight relationship between 
      temporal order of allelic replication and allelic mode of expression, the 
      modified order of allelic replication observed in nonmalignant cells of 
      individuals diagnosed with cancer represents a novel genetic alteration 
      associated with malignancy. This alteration detected by simple cytogenetic means, 
      applied to peripheral blood lymphocytes, offers a potential test for cancer 
      identification. Genes Chromosomes Cancer 27:270-277, 2000.
CI  - Copyright 2000 Wiley-Liss, Inc.
FAU - Dotan, Z A
AU  - Dotan ZA
AD  - Department of Human Genetics, Sackler School of Medicine, Tel-Aviv University, 
      Tel-Aviv, Israel.
FAU - Dotan, A
AU  - Dotan A
FAU - Litmanovitch, T
AU  - Litmanovitch T
FAU - Ravia, Y
AU  - Ravia Y
FAU - Oniashvili, N
AU  - Oniashvili N
FAU - Leibovitch, I
AU  - Leibovitch I
FAU - Ramon, J
AU  - Ramon J
FAU - Avivi, L
AU  - Avivi L
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Genes Chromosomes Cancer
JT  - Genes, chromosomes & cancer
JID - 9007329
RN  - 0 (DNA, Neoplasm)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - *Alleles
MH  - Carcinoma, Renal Cell/*genetics/pathology
MH  - Cell Count
MH  - DNA Replication/*genetics
MH  - DNA, Neoplasm/biosynthesis
MH  - Humans
MH  - Kidney Neoplasms/*genetics/pathology
MH  - Lymphocytes/*metabolism/pathology
MH  - Male
MH  - Middle Aged
MH  - S Phase/genetics
EDAT- 2000/02/19 09:00
MHDA- 2000/03/11 09:00
CRDT- 2000/02/19 09:00
PHST- 2000/02/19 09:00 [pubmed]
PHST- 2000/03/11 09:00 [medline]
PHST- 2000/02/19 09:00 [entrez]
AID - 10.1002/(SICI)1098-2264(200003)27:3<270::AID-GCC7>3.0.CO;2-7 [pii]
PST - ppublish
SO  - Genes Chromosomes Cancer. 2000 Mar;27(3):270-7.