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FHIT and FRA3B 3p14.2 allele loss are common in lung cancer and preneoplastic bronchial lesions and are associated with cancer-related FHIT cDNA splicing aberrations.

Publication ,  Journal Article
Fong, KM; Biesterveld, EJ; Virmani, A; Wistuba, I; Sekido, Y; Bader, SA; Ahmadian, M; Ong, ST; Rassool, FV; Zimmerman, PV; Giaccone, G ...
Published in: Cancer Res
June 1, 1997

We evaluated primary lung cancers, tumor cell lines, and preneoplastic bronchial lesions for molecular genetic abnormalities in the candidate tumor suppressor gene FHIT, which spans the FRA3B fragile site at 3p14.2. 3p14.2 allele loss was very frequent in 32 lung cancer cell lines [100% of small cell lung cancer and 88% of non-small cell lung cancer (NSCLC)] and 108 primary NSCLC cancers (45%), with numerous breakpoints indicating involvement of several distinct regions in the FRA3B site. 3p14 allele loss was least frequent in the adenocarcinoma subtype and occurred at the relatively late carcinoma in situ stage of preneoplastic bronchial lesions found in NSCLC patients. Homozygous deletions within the FHIT/FRA3B region were found in 6 of 135 (4.4%) thoracic cancer cell lines. Northern blot showed low or absent FHIT expression in most thoracic cancer cell lines tested, whereas reverse transcription-PCR showed that 59-62% exhibited aberrant FHIT transcripts but nearly always (93-100%) also expressing the wild-type transcripts. Aberrant transcripts included precise deletions of FHIT exons, insertion of non-FHIT sequences between exons and insertions replacing exons. Complete open reading frame single-strand conformational polymorphism analysis of 102 lung cancer cDNAs revealed only one nonsplicing mutation. Normal cells including bronchial epithelium, lung, and trachea expressed wild-type FHIT transcript and a variant transcript deleted for exon 8 but not the other aberrant transcripts, arguing against exon 8-deleted FHIT transcripts being tumor specific. Our findings support the conclusion that FHIT/FRA3B abnormalities are associated with lung cancer pathogenesis but that FHIT abnormalities differ from the types of mutations and lack of wild-type transcript found in classic tumor suppressor genes, and functional studies are needed to define the role of FHIT in thoracic tumorigenesis.

Duke Scholars

Published In

Cancer Res

ISSN

0008-5472

Publication Date

June 1, 1997

Volume

57

Issue

11

Start / End Page

2256 / 2267

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Transcription, Genetic
  • Sequence Deletion
  • Sequence Analysis, DNA
  • RNA Splicing
  • Proteins
  • Precancerous Conditions
  • Polymorphism, Single-Stranded Conformational
  • Polymorphism, Genetic
  • Polymerase Chain Reaction
 

Citation

APA
Chicago
ICMJE
MLA
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Fong, K. M., Biesterveld, E. J., Virmani, A., Wistuba, I., Sekido, Y., Bader, S. A., … Minna, J. D. (1997). FHIT and FRA3B 3p14.2 allele loss are common in lung cancer and preneoplastic bronchial lesions and are associated with cancer-related FHIT cDNA splicing aberrations. Cancer Res, 57(11), 2256–2267.
Fong, K. M., E. J. Biesterveld, A. Virmani, I. Wistuba, Y. Sekido, S. A. Bader, M. Ahmadian, et al. “FHIT and FRA3B 3p14.2 allele loss are common in lung cancer and preneoplastic bronchial lesions and are associated with cancer-related FHIT cDNA splicing aberrations.Cancer Res 57, no. 11 (June 1, 1997): 2256–67.
Fong KM, Biesterveld EJ, Virmani A, Wistuba I, Sekido Y, Bader SA, et al. FHIT and FRA3B 3p14.2 allele loss are common in lung cancer and preneoplastic bronchial lesions and are associated with cancer-related FHIT cDNA splicing aberrations. Cancer Res. 1997 Jun 1;57(11):2256–67.
Fong KM, Biesterveld EJ, Virmani A, Wistuba I, Sekido Y, Bader SA, Ahmadian M, Ong ST, Rassool FV, Zimmerman PV, Giaccone G, Gazdar AF, Minna JD. FHIT and FRA3B 3p14.2 allele loss are common in lung cancer and preneoplastic bronchial lesions and are associated with cancer-related FHIT cDNA splicing aberrations. Cancer Res. 1997 Jun 1;57(11):2256–2267.

Published In

Cancer Res

ISSN

0008-5472

Publication Date

June 1, 1997

Volume

57

Issue

11

Start / End Page

2256 / 2267

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Transcription, Genetic
  • Sequence Deletion
  • Sequence Analysis, DNA
  • RNA Splicing
  • Proteins
  • Precancerous Conditions
  • Polymorphism, Single-Stranded Conformational
  • Polymorphism, Genetic
  • Polymerase Chain Reaction