High prevalence of p53 exon 4 mutations in soft tissue sarcoma

被引:34
作者
Das, Parimal
Kotilingam, Dhanasekaran
Korchin, Borys
Liu, Jeuhui
Yu, Dihua
Lazar, Alexander J.
Pollock, Raphael E.
Lev, Dina
机构
[1] Univ Texas, MD Anderson Canc Ctr, Dept Canc Biol, Unit 1104, Houston, TX 77030 USA
[2] Univ Texas, MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA
[3] Univ Texas, MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA
关键词
soft tissue sarcoma; p53; mutations; exon; 4; sequencing; immunohistochemistry;
D O I
10.1002/cncr.22680
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
BACKGROUND. p53 is the most commonly mutated gene in cancer, including soft tissue sarcoma (STS). The authors characterized p53 alterations (protein accumulation and gene mutation) in STS to evaluate possible associations with patient outcomes. METHODS. Thirty-one STS specimens (multiple histologies) were analyzed by p53 immunohistochemistry (IHC) and direct DNA sequencing of p53 exons 2-11 and then correlated with outcomes. RESULTS. Direct p53 sequencing detected mutations in 10 of 31 STSs; 7 of 10 were missense mutations, whereas 3 of 10 were either insertions or frameshift mutations, leading to nonfunctional truncated p53; 7 of these p53 mutations have not been previously described. Four p53 exon 4 mutations were identified, a p53 region previously unknown to be mutation prone. Eighteen of the 31 specimens expressed p53 when the authors used the clinical IHC assay of their institution. Interassay concordance of 48% was observed; only 6 of 10 sequencing-identified p53 mutated specimens exhibited nuclear p53 protein expression by IHC, whereas 12 of 18 specimens exhibiting p53 protein expression by IHC harbored sequencing-identified wild-type p53. Decreased survival was observed in STS patients bearing sequencing-identified mutated p53 versus wild-type p53, as was a correlation between IHC-determined nuclear p53 protein expression and decreased survival. CONCLUSIONS. p53 protein stabilization and p53 mutation frequently occur in STS, and both suggest worse outcomes for patients so affected. However, increased p53 protein expression does not necessarily indicate p53 gene mutation. The high incidence of exon 4 mutations found in STS suggests that p53 sequencing should not be limited to the core DNA binding domain.
引用
收藏
页码:2323 / 2333
页数:11
相关论文
共 47 条
  • [1] ANDREASSEN A, 1993, CANCER RES, V53, P468
  • [2] p53 gene mutation:: software and database
    Béroud, C
    Soussi, T
    [J]. NUCLEIC ACIDS RESEARCH, 1998, 26 (01) : 200 - 204
  • [3] Pulmonary metastases from soft tissue sarcoma - Analysis of patterns of disease and postmetastasis survival
    Billingsley, KG
    Burt, ME
    Jara, E
    Ginsberg, RJ
    Woodruff, JM
    Leung, DHY
    Brennan, MF
    [J]. ANNALS OF SURGERY, 1999, 229 (05) : 602 - 612
  • [4] Billingsley KG, 1999, CANCER, V85, P389, DOI 10.1002/(SICI)1097-0142(19990115)85:2<389::AID-CNCR17>3.0.CO
  • [5] 2-J
  • [6] CARIELLO NF, 1994, NUCLEIC ACIDS RES, V22, P3549
  • [7] Casey G, 1996, ONCOGENE, V13, P1971
  • [8] DETECTION OF TP53 GENE-MUTATIONS IN HUMAN SARCOMAS
    CASTRESANA, JS
    RUBIO, MP
    GOMEZ, L
    KREICBERGS, A
    ZETTERBERG, A
    BARRIOS, C
    [J]. EUROPEAN JOURNAL OF CANCER, 1995, 31A (05) : 735 - 738
  • [9] Gain of function of mutant p53: The mutant p53/NF-Y protein complex reveals an aberrant transcriptional mechanism of cell cycle regulation
    Di Agostino, Silvia
    Strano, Sabrina
    Emiliozzi, Velia
    Zerbini, Valentina
    Mottolese, Farcella
    Sacchi, Ada
    Blandino, Giovanni
    Piaggio, Giulia
    [J]. CANCER CELL, 2006, 10 (03) : 191 - 202
  • [10] Gooley TA, 1999, STAT MED, V18, P695, DOI 10.1002/(SICI)1097-0258(19990330)18:6<695::AID-SIM60>3.3.CO