PMID- 9349498
OWN - NLM
STAT- MEDLINE
DCOM- 19971113
LR  - 20071114
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 15
IP  - 14
DP  - 1997 Oct 2
TI  - Frequent deletions of FHIT and FRA3B in Barrett's metaplasia and esophageal 
      adenocarcinomas.
PG  - 1653-9
AB  - The FHIT gene, which spans the common fragile site FRA3B, has been shown to 
      produce aberrant transcripts in a variety of tumor types. Homozygous deletions 
      within the FHIT locus have been detected only in tumor-derived cell lines and LOH 
      has been described in numerous primary tumors. Based on these findings and its 
      location on 3p, FHIT has been proposed as a tumor suppressor gene. To further 
      study the relationship of FRA3B to the findings regarding the FHIT gene and to 
      determine the extent of FHIT mRNA alterations in early stages of tumor 
      development, the status of the FHIT gene was evaluated in the premalignant 
      condition of Barrett's esophagus and associated esophageal adenocarcinomas. FHIT 
      expression was investigated by RT-PCR in normal esophageal, Barrett's metaplasia 
      and adenocarcinoma tissues from 15 patients. Alterations of FHIT transcripts were 
      observed in 12/14 (86%) of Barrett's metaplasia and in 14/15 (93%) of the 
      adenocarcinomas from the same patients. Characterization of the altered 
      transcripts revealed FHIT mRNA lacking one or more exons, with deletion of exons 
      5-7 being most frequent. Analysis of genomic DNA from 20 patients showed 
      homozygous deletions involving exon 5 of FHIT in 4/20 (20%) esophageal 
      adenocarcinomas, and 7/20 (35%) tumors demonstrated hemizygous loss. Genomic 
      deletions also involved the BE758-6 locus, indicating that a large region is 
      deleted. Fluorescence in situ hybridization (FISH) analysis demonstrated that 
      this region of deletion is localized within FRA3B. Our results extend the range 
      of tumor types in which altered FHIT transcripts have been demonstrated and show 
      that these alterations can be seen in the premalignant stage of esophageal tumor 
      development. These results indicate that the fragility and recombination-prone 
      nature of FRA3B is related to tumor-specific chromosomal instability affecting 
      the FHIT gene in esophageal adenocarcinoma development.
FAU - Michael, D
AU  - Michael D
AD  - Department of Human Genetics, University of Michigan, Ann Arbor 48109, USA.
FAU - Beer, D G
AU  - Beer DG
FAU - Wilke, C W
AU  - Wilke CW
FAU - Miller, D E
AU  - Miller DE
FAU - Glover, T W
AU  - Glover TW
LA  - eng
GR  - CA 43222/CA/NCI NIH HHS/United States
GR  - CA 71606/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  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA, Neoplasm)
RN  - 0 (fragile histidine triad protein)
RN  - EC 3.6.- (Acid Anhydride Hydrolases)
SB  - IM
MH  - *Acid Anhydride Hydrolases
MH  - Adenocarcinoma/*genetics
MH  - Barrett Esophagus/*genetics
MH  - Chromosome Fragile Sites
MH  - *Chromosome Fragility
MH  - Chromosome Mapping
MH  - Chromosomes, Human, Pair 3
MH  - Esophageal Neoplasms/*genetics
MH  - Gene Deletion
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - *Neoplasm Proteins
MH  - Proteins/*genetics
MH  - RNA, Messenger/genetics
MH  - RNA, Neoplasm/genetics
EDAT- 1998/02/12 00:00
MHDA- 1998/02/12 00:01
CRDT- 1998/02/12 00:00
PHST- 1998/02/12 00:00 [pubmed]
PHST- 1998/02/12 00:01 [medline]
PHST- 1998/02/12 00:00 [entrez]
AID - 10.1038/sj.onc.1201330 [doi]
PST - ppublish
SO  - Oncogene. 1997 Oct 2;15(14):1653-9. doi: 10.1038/sj.onc.1201330.