P53 gene mutations:: Case study of a clinical marker for solid tumors

被引:64
作者
Liu, MC [1 ]
Gelmann, EP [1 ]
机构
[1] Georgetown Univ, Lombardi Canc Ctr, Dept Oncol, Sch Med, Washington, DC 20007 USA
关键词
D O I
10.1053/sonc.2002.32900
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
P53 is a tumor-suppressor gene that codes for a multi-functional DNA-binding protein involved in cell cycle arrest, DNA repair, differentiation, and apoptosis. The P53 gene is mutated in approximately 50% of human cancers and in germline DNA of families with inherited cancer syndromes. The role of P53 mutations in the program of carcinogenic genetic alterations differs among tumor sites ranging from the earliest mutations that can be detected in premalignant cells to mutations that trigger malignant transformation of a benign neoplasm. P53 mutations can cause expression of abnormal proteins or result in complete absence of P53 expression. For these reasons the role of P53 genetic disruption has different implications in different tumor types and may vary depending on the effect of the mutation on P53 protein function. Immunohistochemical detection of P53, commonly used as a surrogate for identification of a mutant gene, has imperfect sensitivity and specificity, further complicating correlations between P53 gene status and clinical outcomes. The presence of P53 mutations has been shown to affect prognosis of some cancers. The identity of P53 mutations can be used to determine tumor clonality. The detection of P53 mutations suggests the severity of premalignant lesions. Evolving technology for more accurate identification of P53 mutations, better understanding of the function of mutant P53 protein, and more detailed analysis of individual tumor types may expand the relevance of P53 gene analysis for clinical outcomes and therapeutic response. Copyright 2002, Elsevier Science (USA). All rights reserved.
引用
收藏
页码:246 / 257
页数:12
相关论文
共 98 条
[1]   Specific P53 mutations are associated with de novo resistance to doxorubicin in breast cancer patients [J].
Aas, T ;
Borresen, AL ;
Geisler, S ;
SmithSorensen, B ;
Johnsen, H ;
Varhaug, JE ;
Akslen, LA ;
Lonning, PE .
NATURE MEDICINE, 1996, 2 (07) :811-814
[2]  
Allred D. C., 1993, BREAST CANCER RES TR, V27, P131
[3]   ASSOCIATION OF P53 PROTEIN EXPRESSION WITH TUMOR-CELL PROLIFERATION RATE AND CLINICAL OUTCOME IN NODE-NEGATIVE BREAST-CANCER [J].
ALLRED, DC ;
CLARK, GM ;
ELLEDGE, R ;
FUQUA, SAW ;
BROWN, RW ;
CHAMNESS, GC ;
OSBORNE, CK ;
MCGUIRE, WL .
JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1993, 85 (03) :200-206
[4]   Clinical response to fluorouracil and p53 [J].
Augenlicht, LH ;
Wadler, S ;
Arango, D .
NEW ENGLAND JOURNAL OF MEDICINE, 2001, 345 (14) :1065-1066
[5]  
BAKER SJ, 1990, CANCER RES, V50, P7717
[6]  
Bauer JJ, 1995, CLIN CANCER RES, V1, P1295
[7]   Elevated levels of apoptosis regulator proteins p53 and bcl-2 are independent prognostic biomarkers in surgically treated clinically localized prostate cancer [J].
Bauer, JJ ;
Sesterhenn, IA ;
Mostofi, FK ;
McLeod, DG ;
Srivastava, S ;
Moul, JW .
JOURNAL OF UROLOGY, 1996, 156 (04) :1511-1516
[8]   Molecular biomarkers for breast cancer prognosis: Coexpression of c-erbB-2 and p53 [J].
Beenken, SW ;
Grizzle, WE ;
Crowe, DR ;
Conner, MG ;
Weiss, HL ;
Sellers, MT ;
Krontiras, H ;
Urist, MM ;
Bland, KI .
ANNALS OF SURGERY, 2001, 233 (05) :630-637
[9]   COMPLETE SEQUENCING OF THE P53 GENE PROVIDES PROGNOSTIC INFORMATION IN BREAST-CANCER PATIENTS, PARTICULARLY IN RELATION TO ADJUVANT SYSTEMIC THERAPY AND RADIOTHERAPY [J].
BERGH, J ;
NORBERG, T ;
SJOGREN, S ;
LINDGREN, A ;
HOLMBERG, L .
NATURE MEDICINE, 1995, 1 (10) :1029-1034
[10]   TP53 MUTATIONS IN PROSTATIC-CANCER - ANALYSIS OF PRETREATMENT AND POSTTREATMENT ARCHIVAL FORMALIN-FIXED TUMOR-TISSUE [J].
BERNER, A ;
GEITVIK, G ;
KARLSEN, F ;
FOSSA, SD ;
NESLAND, JM ;
BORRESEN, AL .
JOURNAL OF PATHOLOGY, 1995, 176 (03) :299-308