Alterations of Fas (Apo-1/CD95) gene in cutaneous malignant melanoma

被引:113
作者
Shin, MS
Park, WS
Kim, SY
Kim, HS
Kang, SJ
Song, KY
Park, JY
Dong, SM
Pi, JH
Oh, RR
Lee, JY
Yoo, NJ
Lee, SH
机构
[1] Catholic Univ Korea, Coll Med, Dept Pathol, Socho Gu, Seoul 137701, South Korea
[2] Catholic Univ Korea, Coll Med, Dept Biochem, Seoul 137701, South Korea
[3] Catholic Univ Korea, Coll Med, Dept Clin Pathol, Seoul 137701, South Korea
[4] Catholic Univ Korea, Coll Med, Canc Res Inst, Seoul 137701, South Korea
[5] Chung Ang Univ, Coll Med, Dept Pathol, Seoul 156756, South Korea
关键词
D O I
10.1016/S0002-9440(10)65434-X
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
Fas (Apo-1/CD95) is a cell-surface receptor involved in cell death signaling, The key role of the Fas system in negative growth regulation has been studied mostly within the immune system, and somatic mutations of Fas gene in cancer patients have been described solely in lymphoid-lineage malignancies, However, many nonlymphoid tumor cells have been found to be resistant to Fas-mediated apoptosis, which suggests that Fas mutations, one of the possible mechanisms for Fas resistance, may be involved in the pathogenesis of nonlymphoid malignancies as well. In this study, we have analyzed the entire coding region and all splice sites of the Fas gene for the detection of the gene mutations in 44 human malignant melanomas in skin by polymerase chain reaction, single-strand conformation polymorphism, and DNA sequencing. Overall, 3 tumors (6.8%) were found to have the Fns mutations, which were all missense variants and identified in the cytoplasmic region (death domain) known to be involved in the transduction of an apoptotic signal, The data presented here suggest that somatic alterations of the Fns gene might Lad to the loss of its apoptotic function and contribute to the pathogenesis of some human malignant melanomas.
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收藏
页码:1785 / 1791
页数:7
相关论文
共 41 条
  • [1] Beltinger C, 1998, BLOOD, V91, P3943
  • [2] Cell surface trafficking of Fas: A rapid mechanism of p53-mediated apoptosis
    Bennett, M
    Macdonald, K
    Chan, SW
    Luzio, JP
    Simari, R
    Weissberg, P
    [J]. SCIENCE, 1998, 282 (5387) : 290 - 293
  • [3] Missense mutations in the Fas gene resulting in autoimmune lymphoproliferative syndrome: A molecular and immunological analysis
    Bettinardi, A
    Brugnoni, D
    QuirosRoldan, E
    Malagoli, A
    LaGrutta, S
    Correra, A
    Notarangelo, LD
    [J]. BLOOD, 1997, 89 (03) : 902 - 909
  • [4] FADD, A NOVEL DEATH DOMAIN-CONTAINING PROTEIN, INTERACTS WITH THE DEATH DOMAIN OF FAS AND INITIATES APOPTOSIS
    CHINNAIYAN, AM
    OROURKE, K
    TEWARI, M
    DIXIT, VM
    [J]. CELL, 1995, 81 (04) : 505 - 512
  • [5] Spontaneous development of plasmacytoid tumors in mice with defective Fas-Fas ligand interactions
    Davidson, WF
    Giese, T
    Fredrickson, TN
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1998, 187 (11) : 1825 - 1838
  • [6] Fas gene mutations in the Canale-Smith syndrome, an inherited lymphoproliferative disorder associated with autoimmunity
    Drappa, J
    Vaishnaw, AK
    Sullivan, KE
    Chu, JL
    Elkon, KB
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 1996, 335 (22) : 1643 - 1649
  • [7] DOMINANT INTERFERING FAS GENE-MUTATIONS IMPAIR APOPTOSIS IN A HUMAN AUTOIMMUNE LYMPHOPROLIFERATIVE SYNDROME
    FISHER, GH
    ROSENBERG, FJ
    STRAUS, SE
    DALE, JK
    MIDDELTON, LA
    LIN, AY
    STROBER, W
    LENARDO, MJ
    PUCK, JM
    [J]. CELL, 1995, 81 (06) : 935 - 946
  • [8] FIUCCI G, 1994, IMMUNOGENETICS, V39, P437
  • [9] Gronbaek K, 1998, BLOOD, V92, P3018
  • [10] Prognostic significance of allelic losses in primary melanoma
    Healy, E
    Belgaid, C
    Takata, M
    Harrison, D
    Zhu, NW
    Burd, DAR
    Rigby, HS
    Matthews, JNS
    Rees, JL
    [J]. ONCOGENE, 1998, 16 (17) : 2213 - 2218