Assessment of the quality and frequency of mutations occurrence in PTEN gene in endometrial carcinomas and hyperplasias

被引:37
作者
Konopka, B
Paszko, Z
Janiec-Jankowska, A
Goluda, M
机构
[1] Maria Sklodowska Curie Mem Canc Ctr, PL-02781 Warsaw, Poland
[2] Inst Oncol, Dept Endocrinol, PL-02781 Warsaw, Poland
[3] Med Acad, Clin Gynecol 2, Wroclaw, Poland
关键词
endometrial carcinoma; endometrial hyperplasia; PTEN gene mutations;
D O I
10.1016/S0304-3835(01)00815-1
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The quality and frequency of mutations in PTEN gene were assessed in 59 carcinomas and 6 hyperplasias of the endometrium in women. Screening for mutations was done in all exons of PTEN gene by the PCR-SSCP analysis and DNA sequencing. Results were correlated with histological status and clinical features of endometrial carcinomas. In 45.8% (27/59) of carcinomas, 36 somatic mutations were detected in PTEN gene. In seven carcinomas, two mutations and in one carcinoma three mutations coexisted simultaneously. Moreover in 33.3% (2/6) of hyperplasia cases mutations were shown. Most identified mutations (57.9%) were present in exons 5 and 8, less frequently in exons 2 (15.8%) and 7 (13.2%) and they were least frequent in exons 1 and 3 (5.3% each). No mutations were found in exons 4, 6 and 9. Of all identified mutations, 73.7% of those resulting in truncated protein were present due to deletions, insertions and nonsense mutations. Missense mutations accounted for 13.2% of mutations and they were present only in exon 5. One point mutation (2.5%) was in intronic splice site. The remaining 10.5% of mutations were neutral polymorphisms. No statistically significant correlation were found between the frequency of PTEN gene mutations and the clinical stage of endometrial carcinomas. However, evident statistically significant, reverse correlation were observed between the frequency of mutations and the grade of morphological differentiation of the diseases (chi(2) = 7.2393, alpha = 0.0071). In conclusion, our data support the view that PTEN gene mutations are frequent events involved in development of endometrial carcinomas in women. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.
引用
收藏
页码:43 / 51
页数:9
相关论文
共 33 条
[1]   Mutational spectra of PTEN/MMAC1 gene: a tumor suppressor with lipid phosphatase activity [J].
Ali, IU ;
Schriml, LM ;
Dean, M .
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1999, 91 (22) :1922-1932
[2]  
Announcements, 1989, Gynecologic Oncology, V35, P125, DOI [DOI 10.1016/0090-8258(89)90027-9, 10.1016/0090-8258(89)90027-9]
[3]   2 PATHOGENETIC TYPES OF ENDOMETRIAL CARCINOMA [J].
BOKHMAN, JV .
GYNECOLOGIC ONCOLOGY, 1983, 15 (01) :10-17
[4]  
Bonneau D, 2000, HUM MUTAT, V16, P109, DOI 10.1002/1098-1004(200008)16:2<109::AID-HUMU3>3.0.CO
[5]  
2-0
[6]   PTEN mutations in endometrial carcinomas: A molecular and clinicopathologic analysis of 38 cases [J].
Bussaglia, E ;
del Rio, E ;
Matias-Guiu, X ;
Prat, J .
HUMAN PATHOLOGY, 2000, 31 (03) :312-317
[7]   PTEN, a unique tumor suppressor gene [J].
Dahia, PLM .
ENDOCRINE-RELATED CANCER, 2000, 7 (02) :115-129
[8]   The multiple roles of PTEN in tumor suppression [J].
Di Cristofano, A ;
Pandolfi, PP .
CELL, 2000, 100 (04) :387-390
[9]  
Gurin CC, 1999, CANCER RES, V59, P462
[10]  
Ikeda T, 2000, ONCOL REP, V7, P323