The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

FHIT  -  fragile histidine triad

Homo sapiens

Synonyms: AP3A hydrolase, AP3Aase, Bis(5'-adenosyl)-triphosphatase, Diadenosine 5',5'''-P1,P3-triphosphate hydrolase, Dinucleosidetriphosphatase, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of FHIT


High impact information on FHIT


Chemical compound and disease context of FHIT


Biological context of FHIT


Anatomical context of FHIT


Associations of FHIT with chemical compounds


Physical interactions of FHIT


Regulatory relationships of FHIT

  • Ubc9-induced inhibition of diadenosine triphosphate hydrolase activity of the putative tumor suppressor protein Fhit [24].
  • Our results therefore reveal a novel molecular mechanism consisting of FHIT-mediated tumor suppression and the interaction of FHIT with other cellular components in the pathways regulating p53 activity [25].
  • The results suggest that the DNA lesions related to the expression of FRA3B induce the long-patch repair and that the low DNA polymerase alpha activity and inefficient repair process during G2 phase is involved in the expression of FRA3B [26].

Other interactions of FHIT

  • Our findings suggest that hypermethylation of the RAR-beta and FHIT may play an important role in the early stage of esophageal squamous cell carcinogenesis [27].
  • Fragile genes as biomarkers: epigenetic control of WWOX and FHIT in lung, breast and bladder cancer [28].
  • None of the other nine candidate genes were methylated in seminomas, but MGMT (44%), APC (29%) and FHIT (29%) were frequently methylated in NSTGCTs [29].
  • Cell lines included those from patients with germline BRCA1 and FHIT gene mutations and others with possible genetic predisposition [30].
  • We have found that in addition to FHIT, expression of the LTF gene from CER1 at 3p21.33-p21.31 was lost in all 9 tumours analyzed [31].

Analytical, diagnostic and therapeutic context of FHIT

  • Samples were reanalyzed for exon loss using PCR; 13 of 30 tumors failed to generate a PCR product, and 20 of 30 tumors were missing at least one FHIT exon or had loss (loss of heterozygosity or deletion) of one microsatellite marker, suggesting that regions of the gene are homozygously deleted [15].
  • Moreover, Western blots revealed that the levels of FHIT prior to and following fragile site induction was unchanged, whereas p53 was found at elevated levels after induction [32].
  • Loss of FHIT expression was associated with a higher proliferation index (ki-67, P=0.007; flow cytometry, P<0.004) and lower apoptotic index (P=0.018) [9].
  • Aberrant transcripts of FHIT and TSG101 using nested RT-PCR were reported in many human tumours [33].
  • Genomic DNA was also analysed by polymerase chain reaction and sequencing (FHIT) or by Southern blotting (TSG101) [19].


  1. Prevalence and distinctive biologic features of flat colorectal adenomas in a North American population. Saitoh, Y., Waxman, I., West, A.B., Popnikolov, N.K., Gatalica, Z., Watari, J., Obara, T., Kohgo, Y., Pasricha, P.J. Gastroenterology (2001) [Pubmed]
  2. The tumor-suppressor gene FHIT is involved in the regulation of apoptosis and in cell cycle control. Sard, L., Accornero, P., Tornielli, S., Delia, D., Bunone, G., Campiglio, M., Colombo, M.P., Gramegna, M., Croce, C.M., Pierotti, M.A., Sozzi, G. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  3. The candidate tumor suppressor gene, RASSF1A, from human chromosome 3p21.3 is involved in kidney tumorigenesis. Dreijerink, K., Braga, E., Kuzmin, I., Geil, L., Duh, F.M., Angeloni, D., Zbar, B., Lerman, M.I., Stanbridge, E.J., Minna, J.D., Protopopov, A., Li, J., Kashuba, V., Klein, G., Zabarovsky, E.R. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  4. Loss of FHIT function in lung cancer and preinvasive bronchial lesions. Sozzi, G., Pastorino, U., Moiraghi, L., Tagliabue, E., Pezzella, F., Ghirelli, C., Tornielli, S., Sard, L., Huebner, K., Pierotti, M.A., Croce, C.M., Pilotti, S. Cancer Res. (1998) [Pubmed]
  5. Allelic deletion analysis of the FHIT gene predicts poor survival in non-small cell lung cancer. Burke, L., Khan, M.A., Freedman, A.N., Gemma, A., Rusin, M., Guinee, D.G., Bennett, W.P., Caporaso, N.E., Fleming, M.V., Travis, W.D., Colby, T.V., Trastek, V., Pairolero, P.C., Tazelaar, H.D., Midthun, D.E., Liotta, L.A., Harris, C.C. Cancer Res. (1998) [Pubmed]
  6. The gene mutated in ataxia-ocular apraxia 1 encodes the new HIT/Zn-finger protein aprataxin. Moreira, M.C., Barbot, C., Tachi, N., Kozuka, N., Uchida, E., Gibson, T., Mendonça, P., Costa, M., Barros, J., Yanagisawa, T., Watanabe, M., Ikeda, Y., Aoki, M., Nagata, T., Coutinho, P., Sequeiros, J., Koenig, M. Nat. Genet. (2001) [Pubmed]
  7. The FHIT gene, spanning the chromosome 3p14.2 fragile site and renal carcinoma-associated t(3;8) breakpoint, is abnormal in digestive tract cancers. Ohta, M., Inoue, H., Cotticelli, M.G., Kastury, K., Baffa, R., Palazzo, J., Siprashvili, Z., Mori, M., McCue, P., Druck, T., Croce, C.M., Huebner, K. Cell (1996) [Pubmed]
  8. The FHIT gene 3p14.2 is abnormal in lung cancer. Sozzi, G., Veronese, M.L., Negrini, M., Baffa, R., Cotticelli, M.G., Inoue, H., Tornielli, S., Pilotti, S., De Gregorio, L., Pastorino, U., Pierotti, M.A., Ohta, M., Huebner, K., Croce, C.M. Cell (1996) [Pubmed]
  9. Loss of FHIT protein expression is related to high proliferation, low apoptosis and worse prognosis in non-small-cell lung cancer. Toledo, G., Sola, J.J., Lozano, M.D., Soria, E., Pardo, J. Mod. Pathol. (2004) [Pubmed]
  10. Loss of Fhit protein expression in high-grade and advanced stage endometrial carcinomas. Yura, Y., Mandai, M., Konishi, I., Hamid, A.A., Tsuruta, Y., Kusakari, T., Fujii, S. Anticancer Res. (2003) [Pubmed]
  11. Successful treatment of primary and disseminated human lung cancers by systemic delivery of tumor suppressor genes using an improved liposome vector. Ramesh, R., Saeki, T., Templeton, N.S., Ji, L., Stephens, L.C., Ito, I., Wilson, D.R., Wu, Z., Branch, C.D., Minna, J.D., Roth, J.A. Mol. Ther. (2001) [Pubmed]
  12. Alterations of the FHIT gene in breast cancer: association with tumor progression and patient survival. Ingvarsson, S., Sigbjornsdottir, B.I., Huiping, C., Jonasson, J.G., Agnarsson, B.A. Cancer Detect. Prev. (2001) [Pubmed]
  13. Increased Sensitivity to Cisplatin in Non-Small Cell Lung Cancer Cell Lines after FHIT Gene Transfer. Andriani, F., Perego, P., Carenini, N., Sozzi, G., Roz, L. Neoplasia (2006) [Pubmed]
  14. Chromosome 3p14 homozygous deletions and sequence analysis of FRA3B. Boldog, F., Gemmill, R.M., West, J., Robinson, M., Robinson, L., Li, E., Roche, J., Todd, S., Waggoner, B., Lundstrom, R., Jacobson, J., Mullokandov, M.R., Klinger, H., Drabkin, H.A. Hum. Mol. Genet. (1997) [Pubmed]
  15. Chromosome 3p14 alterations in lung cancer: evidence that FHIT exon deletion is a target of tobacco carcinogens and asbestos. Nelson, H.H., Wiencke, J.K., Gunn, L., Wain, J.C., Christiani, D.C., Kelsey, K.T. Cancer Res. (1998) [Pubmed]
  16. The FHIT gene product is highly expressed in the cytoplasm of renal tubular epithelium and is down-regulated in kidney cancers. Xiao, G.H., Jin, F., Klein-Szanto, A.J., Goodrow, T.L., Linehan, M.W., Yeung, R.S. Am. J. Pathol. (1997) [Pubmed]
  17. Aberrant splicing of the TSG101 and FHIT genes occurs frequently in multiple malignancies and in normal tissues and mimics alterations previously described in tumours. Gayther, S.A., Barski, P., Batley, S.J., Li, L., de Foy, K.A., Cohen, S.N., Ponder, B.A., Caldas, C. Oncogene (1997) [Pubmed]
  18. Loss of FHIT expression in breast cancer is correlated with poor prognostic markers. Arun, B., Kilic, G., Yen, C., Foster, B., Yardley, D.A., Gaynor, R., Ashfaq, R. Cancer Epidemiol. Biomarkers Prev. (2005) [Pubmed]
  19. FHIT and TSG101 in thyroid tumours: aberrant transcripts reflect rare abnormal RNA processing events of uncertain pathogenetic or clinical significance. McIver, B., Grebe, S.K., Wang, L., Hay, I.D., Yokomizo, A., Liu, W., Goellner, J.R., Grant, C.S., Smith, D.I., Eberhardt, N.L. Clin. Endocrinol. (Oxf) (2000) [Pubmed]
  20. Alterations of FHIT gene and P16 gene in nickel transformed human bronchial epithelial cells. Ji, W.D., Chen, J.K., Lu, J.C., Wu, Z.L., Yi, F., Feng, S.M. Biomed. Environ. Sci. (2006) [Pubmed]
  21. Association of allelic loss at the FHIT locus and p53 alterations with tumour kinetics and chromosomal instability in non-small cell lung carcinomas (NSCLCs). Garinis, G.A., Gorgoulis, V.G., Mariatos, G., Zacharatos, P., Kotsinas, A., Liloglou, T., Foukas, P., Kanavaros, P., Kastrinakis, N.G., Vassilakopoulos, T., Vogiatzi, T., Field, J.K., Kittas, C. J. Pathol. (2001) [Pubmed]
  22. Crystal structures of HINT demonstrate that histidine triad proteins are GalT-related nucleotide-binding proteins. Brenner, C., Garrison, P., Gilmour, J., Peisach, D., Ringe, D., Petsko, G.A., Lowenstein, J.M. Nat. Struct. Biol. (1997) [Pubmed]
  23. Effect of exogenous E2F-1 on the expression of common chromosome fragile site genes, FHIT and WWOX. Ishii, H., Mimori, K., Vecchione, A., Sutheesophon, K., Fujiwara, T., Mori, M., Furukawa, Y. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  24. Ubc9-induced inhibition of diadenosine triphosphate hydrolase activity of the putative tumor suppressor protein Fhit. Golebiowski, F., Szulc, A., Szutowicz, A., Pawelczyk, T. Arch. Biochem. Biophys. (2004) [Pubmed]
  25. Synergistic tumor suppression by coexpression of FHIT and p53 coincides with FHIT-mediated MDM2 inactivation and p53 stabilization in human non-small cell lung cancer cells. Nishizaki, M., Sasaki, J., Fang, B., Atkinson, E.N., Minna, J.D., Roth, J.A., Ji, L. Cancer Res. (2004) [Pubmed]
  26. The effect of 1-beta-D-arabinofuranosyl-cytosine on the expression of the common fragile site at 3p14. Li, X.Z., Yan, Z.A., Zhou, X.T. Hum. Genet. (1986) [Pubmed]
  27. Allele loss and promoter hypermethylation of VHL, RAR-beta, RASSF1A, and FHIT tumor suppressor genes on chromosome 3p in esophageal squamous cell carcinoma. Kuroki, T., Trapasso, F., Yendamuri, S., Matsuyama, A., Alder, H., Mori, M., Croce, C.M. Cancer Res. (2003) [Pubmed]
  28. Fragile genes as biomarkers: epigenetic control of WWOX and FHIT in lung, breast and bladder cancer. Iliopoulos, D., Guler, G., Han, S.Y., Johnston, D., Druck, T., McCorkell, K.A., Palazzo, J., McCue, P.A., Baffa, R., Huebner, K. Oncogene (2005) [Pubmed]
  29. Frequent epigenetic inactivation of the RASSF1A tumour suppressor gene in testicular tumours and distinct methylation profiles of seminoma and nonseminoma testicular germ cell tumours. Honorio, S., Agathanggelou, A., Wernert, N., Rothe, M., Maher, E.R., Latif, F. Oncogene (2003) [Pubmed]
  30. Characterization of paired tumor and non-tumor cell lines established from patients with breast cancer. Gazdar, A.F., Kurvari, V., Virmani, A., Gollahon, L., Sakaguchi, M., Westerfield, M., Kodagoda, D., Stasny, V., Cunningham, H.T., Wistuba, I.I., Tomlinson, G., Tonk, V., Ashfaq, R., Leitch, A.M., Minna, J.D., Shay, J.W. Int. J. Cancer (1998) [Pubmed]
  31. Down regulation of 3p genes, LTF, SLC38A3 and DRR1, upon growth of human chromosome 3-mouse fibrosarcoma hybrids in severe combined immunodeficiency mice. Kholodnyuk, I.D., Kozireva, S., Kost-Alimova, M., Kashuba, V., Klein, G., Imreh, S. Int. J. Cancer (2006) [Pubmed]
  32. Induction of the common fragile site FRA3B does not affect FHIT expression. Michael, D., Rajewsky, M.F. Oncogene (2001) [Pubmed]
  33. Aberrant transcripts of FHIT, TSG101 and PTEN/MMAC1 genes in normal peripheral mononuclear cells. Wang, N.M., Chang, J.G., Liu, T.C., Lin, S.F., Peng, C.T., Tsai, F.J., Tsai, C.H. Int. J. Oncol. (2000) [Pubmed]
WikiGenes - Universities