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. 1996 Sep 3;93(18):9770–9775. doi: 10.1073/pnas.93.18.9770

FHIT gene alterations in head and neck squamous cell carcinomas.

L Virgilio 1, M Shuster 1, S M Gollin 1, M L Veronese 1, M Ohta 1, K Huebner 1, C M Croce 1
PMCID: PMC38504  PMID: 8790406

Abstract

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.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ah-See K. W., Cooke T. G., Pickford I. R., 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] [Google Scholar]
  2. Cairns P., Polascik T. J., Eby Y., Tokino K., Califano J., Merlo A., Mao L., Herath J., Jenkins R., Westra W. Frequency of homozygous deletion at p16/CDKN2 in primary human tumours. Nat Genet. 1995 Oct;11(2):210–212. doi: 10.1038/ng1095-210. [DOI] [PubMed] [Google Scholar]
  3. Franceschi S., Talamini R., Barra S., Barón A. E., 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] [Google Scholar]
  4. Glover T. W., Coyle-Morris J. F., Li F. P., Brown R. S., Berger C. S., Gemmill R. M., 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. doi: 10.1016/0165-4608(88)90013-1. [DOI] [PubMed] [Google Scholar]
  5. Ishwad C. S., Ferrell R. E., Rossie K. N., Appel B. N., Johnson J. T., Myers E. N., Law J. C., Srivastava S., Gollin S. M. 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. doi: 10.1002/(SICI)1097-0215(19960220)69:1<1::AID-IJC1>3.0.CO;2-8. [DOI] [PubMed] [Google Scholar]
  6. Jones M. H., Nakamura Y. Deletion mapping of chromosome 3p in female genital tract malignancies using microsatellite polymorphisms. Oncogene. 1992 Aug;7(8):1631–1634. [PubMed] [Google Scholar]
  7. Kastury K., Baffa R., Druck T., Ohta M., Cotticelli M. G., Inoue H., Negrini M., Rugge M., Huang D., Croce C. M. 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] [Google Scholar]
  8. Kok K., Osinga J., Carritt B., Davis M. B., van der Hout A. H., van der Veen A. Y., Landsvater R. M., de Leij L. F., Berendsen H. H., Postmus P. E. 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. doi: 10.1038/330578a0. [DOI] [PubMed] [Google Scholar]
  9. Lichter P., Ried T. Molecular analysis of chromosome aberrations. In situ hybridization. Methods Mol Biol. 1994;29:449–478. doi: 10.1385/0-89603-289-2:449. [DOI] [PubMed] [Google Scholar]
  10. Mao L., Lee J. S., Fan Y. H., Ro J. Y., Batsakis J. G., Lippman S., Hittelman W., Hong W. K. 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. doi: 10.1038/nm0696-682. [DOI] [PubMed] [Google Scholar]
  11. Nawroz H., van der Riet P., Hruban R. H., Koch W., Ruppert J. M., Sidransky D. Allelotype of head and neck squamous cell carcinoma. Cancer Res. 1994 Mar 1;54(5):1152–1155. [PubMed] [Google Scholar]
  12. Naylor S. L., Johnson B. E., Minna J. D., Sakaguchi A. Y. Loss of heterozygosity of chromosome 3p markers in small-cell lung cancer. Nature. 1987 Oct 1;329(6138):451–454. doi: 10.1038/329451a0. [DOI] [PubMed] [Google Scholar]
  13. Negrini M., Monaco C., Vorechovsky I., Ohta M., Druck T., Baffa R., Huebner K., Croce C. M. The FHIT gene at 3p14.2 is abnormal in breast carcinomas. Cancer Res. 1996 Jul 15;56(14):3173–3179. [PubMed] [Google Scholar]
  14. Nobori T., Miura K., Wu D. J., Lois A., Takabayashi K., Carson D. A. Deletions of the cyclin-dependent kinase-4 inhibitor gene in multiple human cancers. Nature. 1994 Apr 21;368(6473):753–756. doi: 10.1038/368753a0. [DOI] [PubMed] [Google Scholar]
  15. Ohta M., Inoue H., Cotticelli M. G., Kastury K., Baffa R., Palazzo J., Siprashvili Z., Mori M., McCue P., Druck T. 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. doi: 10.1016/s0092-8674(00)81034-x. [DOI] [PubMed] [Google Scholar]
  16. Parker S. L., Tong T., Bolden S., Wingo P. A. Cancer statistics, 1996. CA Cancer J Clin. 1996 Jan-Feb;46(1):5–27. doi: 10.3322/canjclin.46.1.5. [DOI] [PubMed] [Google Scholar]
  17. Roz L., Wu C. L., 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] [Google Scholar]
  18. 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] [Google Scholar]
  19. Smeets D. F., Scheres J. M., Hustinx T. W. The most common fragile site in man is 3p14. Hum Genet. 1986 Mar;72(3):215–220. doi: 10.1007/BF00291880. [DOI] [PubMed] [Google Scholar]
  20. Sozzi G., Alder H., Tornielli S., Corletto V., Baffa R., Veronese M. L., Negrini M., Pilotti S., Pierotti M. A., Huebner K. Aberrant FHIT transcripts in Merkel cell carcinoma. Cancer Res. 1996 Jun 1;56(11):2472–2474. [PubMed] [Google Scholar]
  21. Sozzi G., Veronese M. L., Negrini M., Baffa R., Cotticelli M. G., Inoue H., Tornielli S., Pilotti S., De Gregorio L., Pastorino U. The FHIT gene 3p14.2 is abnormal in lung cancer. Cell. 1996 Apr 5;85(1):17–26. doi: 10.1016/s0092-8674(00)81078-8. [DOI] [PubMed] [Google Scholar]
  22. Sutherland G. R. Chromosomal fragile sites. Genet Anal Tech Appl. 1991 Sep;8(6):161–166. doi: 10.1016/1050-3862(91)90056-w. [DOI] [PubMed] [Google Scholar]
  23. Wu C. L., Sloan P., Read A. P., 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] [Google Scholar]
  24. Wynder E. L., Stellman S. D. Comparative epidemiology of tobacco-related cancers. Cancer Res. 1977 Dec;37(12):4608–4622. [PubMed] [Google Scholar]
  25. 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. doi: 10.1073/pnas.84.24.9252. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. 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] [Google Scholar]
  27. Yunis J. J., Soreng A. L. Constitutive fragile sites and cancer. Science. 1984 Dec 7;226(4679):1199–1204. doi: 10.1126/science.6239375. [DOI] [PubMed] [Google Scholar]
  28. Zhang S. Y., Klein-Szanto A. J., Sauter E. R., Shafarenko M., Mitsunaga S., Nobori T., Carson D. A., Ridge J. A., Goodrow T. L. 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] [Google Scholar]

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