Skip to main content
Journal cover image

Precise localization of the FHIT gene to the common fragile site at 3p14.2 (FRA3B) and characterization of homozygous deletions within FRA3B that affect FHIT transcription in tumor cell lines.

Publication ,  Journal Article
Ong, ST; Fong, KM; Bader, SA; Minna, JD; Le Beau, MM; McKeithan, TW; Rassool, FV
Published in: Genes Chromosomes Cancer
September 1997

Chromosomal or allelic losses at 3p14 are common in a variety of human tumors, including those of the lung, breast, kidney, and head and neck. This suggests the existence of a tumor suppressor gene in this band. A promising candidate is the recently cloned FHIT gene, which spans the common fragile site, FRA3B, at 3p14.2. We previously identified a region of fragility at 3p14.2 (FRA3B) of > 85 kb by cloning DNA flanking pSV2neo integrations and constructed a partial genomic contig of the region. Using probes from the contig, we tested for deletions within this region in DNA from 105 human tumor cell lines, predominantly derived from lung cancers. We identified one gastric and four lung cancer cell lines with homozygous interstitial deletions involving the FRA3B region. The deletion in one lung cancer cell line lies entirely within our contig and is < 65 kb. We have identified, cloned, and sequenced this breakpoint junction. We have also shown that our probes lie within intron S of the FHIT gene and, furthermore, that exon 5 is located approximately 1 kb from one of our probes and, thus, lies within the region of fragility. Two lines with entirely intronic deletions yield FHIT transcripts of normal size. In one of these, this was the sole transcript identified. In the other line, an FHIT transcript completely normal in sequence was accompanied by two larger abnormal transcripts. These results leave open the possibility that some homozygous deletions within the FHIT gene are without phenotypic effect and result from genetic instability of this region. However, taken together, our results provide evidence that breakage and rearrangement within the FRA3B fragile site sequences result in alterations of FHIT and are likely to be involved in carcinogenesis.

Duke Scholars

Published In

Genes Chromosomes Cancer

DOI

ISSN

1045-2257

Publication Date

September 1997

Volume

20

Issue

1

Start / End Page

16 / 23

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Sequence Analysis, DNA
  • Sequence Alignment
  • RNA, Neoplasm
  • Proteins
  • Polymerase Chain Reaction
  • Oncology & Carcinogenesis
  • Neoplasm Proteins
  • Molecular Sequence Data
  • Humans
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Ong, S. T., Fong, K. M., Bader, S. A., Minna, J. D., Le Beau, M. M., McKeithan, T. W., & Rassool, F. V. (1997). Precise localization of the FHIT gene to the common fragile site at 3p14.2 (FRA3B) and characterization of homozygous deletions within FRA3B that affect FHIT transcription in tumor cell lines. Genes Chromosomes Cancer, 20(1), 16–23. https://doi.org/10.1002/(sici)1098-2264(199709)20:1<16::aid-gcc3>3.0.co;2-c
Ong, S. T., K. M. Fong, S. A. Bader, J. D. Minna, M. M. Le Beau, T. W. McKeithan, and F. V. Rassool. “Precise localization of the FHIT gene to the common fragile site at 3p14.2 (FRA3B) and characterization of homozygous deletions within FRA3B that affect FHIT transcription in tumor cell lines.Genes Chromosomes Cancer 20, no. 1 (September 1997): 16–23. https://doi.org/10.1002/(sici)1098-2264(199709)20:1<16::aid-gcc3>3.0.co;2-c.
Ong, S. T., et al. “Precise localization of the FHIT gene to the common fragile site at 3p14.2 (FRA3B) and characterization of homozygous deletions within FRA3B that affect FHIT transcription in tumor cell lines.Genes Chromosomes Cancer, vol. 20, no. 1, Sept. 1997, pp. 16–23. Pubmed, doi:10.1002/(sici)1098-2264(199709)20:1<16::aid-gcc3>3.0.co;2-c.
Journal cover image

Published In

Genes Chromosomes Cancer

DOI

ISSN

1045-2257

Publication Date

September 1997

Volume

20

Issue

1

Start / End Page

16 / 23

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Sequence Analysis, DNA
  • Sequence Alignment
  • RNA, Neoplasm
  • Proteins
  • Polymerase Chain Reaction
  • Oncology & Carcinogenesis
  • Neoplasm Proteins
  • Molecular Sequence Data
  • Humans