Mutations Fas gene

These finding require further investigation to determine the relationship between tumor biology and defects of Fas-mediated apoptosis. Indeed, Fas gene mutations were first reported in Ipr and mice (A2, L5, W1) and were recently reported in... 

If Fas gene mutations are significant in tumor biology, mutations may be clustered in the most important region of the gene. Accordingly, the hot spot of the mutations in cancers and the relationship between the mutation domain and the functional impairment are discussed in this section. 

Fig. 7. The distribution of Fas gene mutations within the coding region. The codon number indicated on the x-axis corresponds to the lower horizontal boxes, which indicate the exon numbers of the Fas gene. Mutations are obviously concentrated in exons 6 and 9, which encode the transmembrane domain and the intracytoplasmic region containing the death-signaling domain, respectively. No mutations have been reported in exons 1 or 5. The numbers on top of the bars (162, 234, 244, 251, and 253) show codons that are mutated at high frequency.

Fas gene mutations (a) lupus-prone mice b) ALPS (see Table 1), SLE (very rare)... 

Drappa J, Vaishnaw AK, Sullivan KA, Chu JL, Elkon KB (1996) Fas gene mutations in the Canale-Smith syndrome, an inherited lymphoproliferative disorder associated with autoimmunity. N Engl J Med, 335 1643-1649. 

Fisher GH, Rosenberg FJ, Straus SE, Dale JK, Middleton LA, Lin AY, Strober W, Leonardo MJ, Puck JM (1995) Dominant interfering Fas gene mutations impair apoptosis in a human autoimmune lymphoproliferative syndrome. Cell, 81 935-946. 

Ramenghi U, Bonissoni S, Migliaretti G, DeFranco S, Bottarel F, Gambaruto C, DiFranco D, Priori R, Conti F, Dianzani I, Valesini G, Merletti F, Dianzani U (2000) Deficiency of the Fas apoptosis pathway without Fas gene mutations is a familial trait predisposing to development of autoimmune diseases and cancer. Blood, 95 3176-3182. 

APOPTOSIS, PART II THE ROLE OF MUTATED Fas GENES IN TUMORIGENESIS... 

The decoy function of aberrant and intact sFas was discussed above now we will review the attenuating mechanism of aberrant mFas for Fas-mediated apoptosis. Data from our ATL studies and the literature indicate several different mechanisms for attenuating Fas-mediated signaling depending on the aberrant structure of the Fas molecule produced by the mutated Fas gene, as shown in Fig. 8. 

B6. Bertoni, R, Conconi, A., Lutrdnari, S., Realini, C., Roggero, E., Baldini, L., Carobbio, S., Cavalli, R, Neri, A., and Zucca, E., Lack of CD95/FAS gene somatic mutations in extranodal, nodal and splenic marginal zone B cell lymphomas. Leukemia 14, 446-448 (2000). 

Mutations in the FAS gene Impaired selftolerance by preventing the elimination of activated peripheral T cells Autoimmune lymphoprolifera-tive syndrome (ALPS) type la... 

Autoimmune lymphoproliferative syndrome (ALPS). Also known as Canale-Smith syndrome. Characterized by lymphadenop-athy, hepatosplenomegaly, autoimmune cytopenias, and hyper-gammaglobulinaemia. Associated with defects in the Fas-FasL apoptosis signalling pathway due to mutations in the Fas gene, the FasL gene, or other genes coding for factors of this pathway. 

Dianzani U, Bragardo M, DiFranco D, Alliaudi C, Scagni P, Buonfiglio D, Redoglia V, Bonissoni S, Correra A, Dianzani I, Ramenghi U (1997) Deficiency of the Fas apoptosis pathway without gene mutations in pediatric patients with autoimmunity/lympho-proliferation. Blood, 89 2871-2879. 

Adachi M, Suematsu S, Kondo T, Ogasawara J, Tanaka T, Yoshida N, Nagata S (1995) Targeted mutation in the Fas gene causes hyperplasia in peripheral lymphoid organs and liver. Nature Genet 11 294-300... 

A fuller understanding of the Fas-FasL interaction is necessary to comprehend better the signaling pathway involved in death receptor-induced apoptosis. Inappropriate expression of Fas and FasL on lymphocytes and other immune cells has previously been documented in patients with HIV infection it has also been implicated in the loss of lymphocytes that characterizes this immunodeficiency syndrome [32]. Conversely, hereditary mutations in the death domain of the Fas gene are known to cause an autoimmune lymphoproliferative syndrome in humans [33]. 

Al. Abdel-Rahman, W., Arends, M., Morris, R., Ramadan, M., and Wyllie, A., Death pathway genes Fas (Apo-l/CD95) and Bik (Nbk) show no mutations in colorectal carcinomas [letterl [see comments]. Cell Death Differ. 6,387—388 (1999). 

B5. Bertoni, R, Concord, A., Carobbio, S., ReaUni, C., Codegoni, A. M., Zucca, E., and CavalU, F., Analysis of Fas/CD95 gene somatic mutations in ovarian cancer cell lines Petter]. Int. J. Cancer 86, 450 (2000). 

T2. Tamiya, S., Ftoh, K., Suzushima, H., Takatsuki, K., and Matsuoka, M., Mutation of CD95 (Fas/Apo-1) gene in adult T-cell leukemia cells. Blood 91, 3935-3942 (1998). 

Araki T, Mohi MG, Ismat FA et al (2004) Mouse model of Noonan syndrome reveals cell type- and gene dosage-dependent effects ofPtpnll mutation. Nat Med 10 849-857... 

---