• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of pnasPNASInfo for AuthorsSubscriptionsAboutThis Article
Proc Natl Acad Sci U S A. Sep 3, 1996; 93(18): 9770–9775.

FHIT gene alterations in head and neck squamous cell carcinomas.


To determine whether the FHIT gene at 3p14.2 is altered in head and neck squamous cell carcinomas (HNSCC), we examined 26 HNSCC cell lines for deletions within the FHIT locus by Southern analysis, for allelic losses of specific exons FHIT by fluorescence in situ hybridization (FISH) and for integrity of FHIT transcripts. Three cell lines exhibited homozygous deletions within the FHIT gene, 55% (15/25) showed the presence of aberrant transcripts, and 65% (13/20) showed the presence of multiple cell populations with losses of different portions of FHIT alleles by FISH of FHIT genomic clones to interphase nuclei. When the data obtained by FISH and by reverse transcriptase-PCR analyses are combined, 22 of 26 cell lines showed alterations of at least one allele of the FHIT gene. Our data indicate that the FHIT gene is disrupted in HNSCCs and hence, loss of FHIT function may be important in the development and/or progression of head and neck cancers.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.4M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Parker SL, Tong T, Bolden S, Wingo PA. Cancer statistics, 1996. CA Cancer J Clin. 1996 Jan-Feb;46(1):5–27. [PubMed]
  • Ah-See KW, Cooke TG, Pickford IR, Soutar D, Balmain A. An allelotype of squamous carcinoma of the head and neck using microsatellite markers. Cancer Res. 1994 Apr 1;54(7):1617–1621. [PubMed]
  • Nawroz H, van der Riet P, Hruban RH, Koch W, Ruppert JM, Sidransky D. Allelotype of head and neck squamous cell carcinoma. Cancer Res. 1994 Mar 1;54(5):1152–1155. [PubMed]
  • Ishwad CS, Ferrell RE, Rossie KN, Appel BN, Johnson JT, Myers EN, Law JC, Srivastava S, Gollin SM. Loss of heterozygosity of the short arm of chromosomes 3 and 9 in oral cancer. Int J Cancer. 1996 Feb 20;69(1):1–4. [PubMed]
  • Nobori T, Miura K, Wu DJ, Lois A, Takabayashi K, Carson DA. Deletions of the cyclin-dependent kinase-4 inhibitor gene in multiple human cancers. Nature. 1994 Apr 21;368(6473):753–756. [PubMed]
  • Cairns P, Polascik TJ, Eby Y, Tokino K, Califano J, Merlo A, Mao L, Herath J, Jenkins R, Westra W, et al. Frequency of homozygous deletion at p16/CDKN2 in primary human tumours. Nat Genet. 1995 Oct;11(2):210–212. [PubMed]
  • Zhang SY, Klein-Szanto AJ, Sauter ER, Shafarenko M, Mitsunaga S, Nobori T, Carson DA, Ridge JA, Goodrow TL. Higher frequency of alterations in the p16/CDKN2 gene in squamous cell carcinoma cell lines than in primary tumors of the head and neck. Cancer Res. 1994 Oct 1;54(19):5050–5053. [PubMed]
  • Kok K, Osinga J, Carritt B, Davis MB, van der Hout AH, van der Veen AY, Landsvater RM, de Leij LF, Berendsen HH, Postmus PE, et al. Deletion of a DNA sequence at the chromosomal region 3p21 in all major types of lung cancer. Nature. 1987 Dec 10;330(6148):578–581. [PubMed]
  • Naylor SL, Johnson BE, Minna JD, Sakaguchi AY. Loss of heterozygosity of chromosome 3p markers in small-cell lung cancer. Nature. 1987 Oct 1;329(6138):451–454. [PubMed]
  • Yokota J, Wada M, Shimosato Y, Terada M, Sugimura T. Loss of heterozygosity on chromosomes 3, 13, and 17 in small-cell carcinoma and on chromosome 3 in adenocarcinoma of the lung. Proc Natl Acad Sci U S A. 1987 Dec;84(24):9252–9256. [PMC free article] [PubMed]
  • Yokoyama S, Yamakawa K, Tsuchiya E, Murata M, Sakiyama S, Nakamura Y. Deletion mapping on the short arm of chromosome 3 in squamous cell carcinoma and adenocarcinoma of the lung. Cancer Res. 1992 Feb 15;52(4):873–877. [PubMed]
  • Sato T, Akiyama F, Sakamoto G, Kasumi F, Nakamura Y. Accumulation of genetic alterations and progression of primary breast cancer. Cancer Res. 1991 Nov 1;51(21):5794–5799. [PubMed]
  • Jones MH, Nakamura Y. Deletion mapping of chromosome 3p in female genital tract malignancies using microsatellite polymorphisms. Oncogene. 1992 Aug;7(8):1631–1634. [PubMed]
  • Sutherland GR. Chromosomal fragile sites. Genet Anal Tech Appl. 1991 Sep;8(6):161–166. [PubMed]
  • Smeets DF, Scheres JM, Hustinx TW. The most common fragile site in man is 3p14. Hum Genet. 1986 Mar;72(3):215–220. [PubMed]
  • Yunis JJ, Soreng AL. Constitutive fragile sites and cancer. Science. 1984 Dec 7;226(4679):1199–1204. [PubMed]
  • Roz L, Wu CL, Porter S, Scully C, Speight P, Read A, Sloan P, Thakker N. Allelic imbalance on chromosome 3p in oral dysplastic lesions: an early event in oral carcinogenesis. Cancer Res. 1996 Mar 15;56(6):1228–1231. [PubMed]
  • Mao L, Lee JS, Fan YH, Ro JY, Batsakis JG, Lippman S, Hittelman W, Hong WK. Frequent microsatellite alterations at chromosomes 9p21 and 3p14 in oral premalignant lesions and their value in cancer risk assessment. Nat Med. 1996 Jun;2(6):682–685. [PubMed]
  • Kastury K, Baffa R, Druck T, Ohta M, Cotticelli MG, Inoue H, Negrini M, Rugge M, Huang D, Croce CM, et al. Potential gastrointestinal tumor suppressor locus at the 3p14.2 FRA3B site identified by homozygous deletions in tumor cell lines. Cancer Res. 1996 Mar 1;56(5):978–983. [PubMed]
  • Ohta M, Inoue H, Cotticelli MG, Kastury K, Baffa R, Palazzo J, Siprashvili Z, Mori M, McCue P, Druck T, et al. The FHIT gene, spanning the chromosome 3p14.2 fragile site and renal carcinoma-associated t(3;8) breakpoint, is abnormal in digestive tract cancers. Cell. 1996 Feb 23;84(4):587–597. [PubMed]
  • Sozzi G, Veronese ML, Negrini M, Baffa R, Cotticelli MG, Inoue H, Tornielli S, Pilotti S, De Gregorio L, Pastorino U, et al. The FHIT gene 3p14.2 is abnormal in lung cancer. Cell. 1996 Apr 5;85(1):17–26. [PubMed]
  • Franceschi S, Talamini R, Barra S, Barón AE, Negri E, Bidoli E, Serraino D, La Vecchia C. Smoking and drinking in relation to cancers of the oral cavity, pharynx, larynx, and esophagus in northern Italy. Cancer Res. 1990 Oct 15;50(20):6502–6507. [PubMed]
  • Wynder EL, Stellman SD. Comparative epidemiology of tobacco-related cancers. Cancer Res. 1977 Dec;37(12):4608–4622. [PubMed]
  • Lichter P, Ried T. Molecular analysis of chromosome aberrations. In situ hybridization. Methods Mol Biol. 1994;29:449–478. [PubMed]
  • Wu CL, Sloan P, Read AP, Harris R, Thakker N. Deletion mapping on the short arm of chromosome 3 in squamous cell carcinoma of the oral cavity. Cancer Res. 1994 Dec 15;54(24):6484–6488. [PubMed]
  • Glover TW, Coyle-Morris JF, Li FP, Brown RS, Berger CS, Gemmill RM, Hecht F. Translocation t(3;8)(p14.2;q24.1) in renal cell carcinoma affects expression of the common fragile site at 3p14(FRA3B) in lymphocytes. Cancer Genet Cytogenet. 1988 Mar;31(1):69–73. [PubMed]
  • Sozzi G, Alder H, Tornielli S, Corletto V, Baffa R, Veronese ML, Negrini M, Pilotti S, Pierotti MA, Huebner K, et al. Aberrant FHIT transcripts in Merkel cell carcinoma. Cancer Res. 1996 Jun 1;56(11):2472–2474. [PubMed]
  • Negrini M, Monaco C, Vorechovsky I, Ohta M, Druck T, Baffa R, Huebner K, Croce CM. The FHIT gene at 3p14.2 is abnormal in breast carcinomas. Cancer Res. 1996 Jul 15;56(14):3173–3179. [PubMed]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • MedGen
    Related information in MedGen
  • OMIM
    OMIM record citing PubMed
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...