PMID- 9788625
OWN - NLM
STAT- MEDLINE
DCOM- 19981106
LR  - 20071114
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 58
IP  - 20
DP  - 1998 Oct 15
TI  - Chromosomal duplication accompanies allelic loss in non-small cell lung 
      carcinoma.
PG  - 4701-7
AB  - Hemizygous deletion in the short (p) arm of chromosome 3 is a common finding in 
      non-small cell lung carcinoma (NSCLC) and is postulated to be a crucial early 
      change in lung tumorigenesis. Yet one of the most frequent nuclear abnormalities 
      in both NSCLC and premalignant bronchial epithelium is increase in chromosomal 
      copy number. Deletion and duplication have not been assessed in the same tumor 
      set by both molecular and cytogenetic methods to determine whether allelic loss 
      correlates with chromosomal duplication in the same tumor cell populations. It is 
      also not established what biological mechanisms might lead to allelic deletion 
      and chromosomal duplication. We have investigated changes in the copy number of 
      chromosome 3 in touch preparations of 38 NSCLCs (19 adenocarcinomas and 19 
      squamous cell carcinomas) using dual-target, dual-color fluorescence in situ 
      hybridization (FISH) assays. Chromosome 3 centromere probe was matched with a 
      3p14.2 probe [intron 4 of the fragile histidine triad (FHIT) gene] and a 3p21.31 
      probe (HSemaIV gene). We then correlated FISH results with results of molecular 
      analyses for allelic losses at loci in the regions to which the FISH probes 
      mapped in 20 of these cases. Although various combinations of FISH abnormalities 
      were sometimes detected within the same specimens, individual cases could be 
      classified according to the predominant FISH pattern, usually with one 
      abnormality present in >60% of tumor cells. Chromosomal duplication, indicated by 
      the presence of more than two centromeric signals, was the most frequent 
      abnormality observed by FISH and was accompanied by loss of specific sequences on 
      3p in approximately one-half of the specimens in which it was observed. The most 
      frequent abnormality observed by molecular analysis was loss of heterozygosity 
      (LOH) in both of the chromosomal regions tested and was demonstrated in 83% of 
      cases with chromosomal duplication. We conclude that LOH may occur in the 
      presence of chromosomal duplication, suggesting that the duplicated chromosome is 
      homozygous. Our findings imply that LOH occurs before chromosomal duplication 
      during lung carcinogenesis.
FAU - Varella-Garcia, M
AU  - Varella-Garcia M
AD  - Division of Medical Oncology, University of Colorado Health Sciences Center, 
      Denver 80262, USA.
FAU - Gemmill, R M
AU  - Gemmill RM
FAU - Rabenhorst, S H
AU  - Rabenhorst SH
FAU - Lotto, A
AU  - Lotto A
FAU - Drabkin, H A
AU  - Drabkin HA
FAU - Archer, P A
AU  - Archer PA
FAU - Franklin, W A
AU  - Franklin WA
LA  - eng
GR  - 5P30 CA 46934/CA/NCI NIH HHS/United States
GR  - P50 CA 58187/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Proteins)
RN  - 0 (fragile histidine triad protein)
RN  - EC 3.6.- (Acid Anhydride Hydrolases)
SB  - IM
MH  - *Acid Anhydride Hydrolases
MH  - Carcinoma, Non-Small-Cell Lung/*genetics
MH  - *Chromosomes, Human, Pair 3
MH  - *Gene Duplication
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - *Loss of Heterozygosity
MH  - Lung Neoplasms/*genetics
MH  - *Neoplasm Proteins
MH  - Proteins/genetics
EDAT- 1998/10/27 00:00
MHDA- 1998/10/27 00:01
CRDT- 1998/10/27 00:00
PHST- 1998/10/27 00:00 [pubmed]
PHST- 1998/10/27 00:01 [medline]
PHST- 1998/10/27 00:00 [entrez]
PST - ppublish
SO  - Cancer Res. 1998 Oct 15;58(20):4701-7.