Single Mutations of the PTEN Gene in Recurrent Ovarian Carcinomas

Abstract

Objective: To establish the role of phosphate and tensin homologue on chromosome 10 (PTEN) mutations in tumorigenesis of the ovary, we determined the mutational spectrum of the PTEN gene in surgical specimens of ovarian carcinomas.

Methods: The study group consisted of 86 ovarian cancer specimens (18 fluids, 68 solid specimens), inclding 30 primary ovarian cancer specimens and 56 of replaced ovarian cancer from women with a median age of 57.9 years and a range of 27-85 years. Each of the nine exons of the PTEN gene was amplified separately by polymerase chain reaction (PCR). Both strands of the PCR products were sequenced directly by standard cycle sequencing procedures and subsequent computer-aided alignments with the wild-type sequence.

Results: In ascitic fluids of two women with recurrence of cancer, we observed mutations: one seven-base-pair insertion at codon 52 (GATGATG) and the other a base-pair substitution resulting in an amino acid change (T1311). We found no mutation in the primary ovarian cancers.

Conclusions: Our data indicate that PTEN mutations have a subordinate role in tumorigenesis of the ovary.

Keywords

PTEN ovarian carcinoma

Get full access to this article

View all access options for this article.

References

1. Lynch HT , Casey MJ , Lynch J , White TEK , Godwin AK . Genetics and ovarian carcinoma. Semin Oncol 1998;25:265-281.

2. DePasquale SE , Giordano A , Donnenfeld AE . The genetics of ovarian cancer: Molecular biology and clinical application. Obstet Gynecol Surve 1998;53:248-256.

3. McCluskey LL , Dubeau L . Biology of ovarian cancer. Curr Opin Oncol 1997;9:465-470.

4. Steck PA , Pershouse MA , Jasser SA , et al. Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancer. Nat Genet 1997;15:356-362.

5. Li J , Yen C , Liaw D , et al. PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science 1997;275:1943-1947.

6. Stambolic V , Suzuki A , de la Pompa JL , et al. Negative regulation of PKB/Akt-dependent cell survival by the tumor suppressor PTEN. Cell 1998;95:29-39.

7. Ramaswamy S , Nakamura N , Vazquez F , et al. Regulation of G1 progression by the PTEN tumor suppressor protein is linked to inhibition of the phosphatidylinositol 3-kinase/Akt pathway. Proc Natl Acad Sci U S A 1999; 96:2110-2115.

8. Myers MP , Pass I , Batty IH , et al. The lipid phosphatase activity of PTEN is critical for tumor suppressor function. Proc Natl Acad Sci U S A 1998;95:13513-13518.

9. Hopkins K . A surprising function for the PTEN tumor suppressor. Science 1998;282:1027-1030.

10.

10. Ali IU , Schriml LM , Dean M . Mutational spectra of PTEN/MMAC1 gene: A tumor suppressor with lipid phosphatase activity. J Natl Cancer Inst 1999;91:1922-1932.

11.

11. Maxwell GL , Risinger JI , Tong B , et al. Mutation of the PTEN tumor suppressor gene is not a feature of ovarian cancers. Gynecol Oncol 1998;70:13-16.

12.

12. Obata K , Morland SJ , Watson RH , et al. Frequent PTEN/MMAC mutations in endometrioid but not serous or mucinous epithelial ovaraian tumors. Cancer Res 1998;58:2095-2097.

13.

13. Teng DH-F , Hu R , Lin H , et al. MMAC1/PTEN mutations in primary tumor specimens and tumor cell lines. Cancer Res 1997;57:5221-5225.

14.

14. Yokomizo A , Tindall DJ , Hartmann L , Jenkins RB , Smith DI , Liu W . Mutation analysis of the putative tumor suppressor PTEN/MMAC1 in human ovarian cancer. Int J Oncol 1998;13:101-105.

15.

15. Tashiro H , Blazes MS , Wu R , et al. Mutations in PTEN are frequent in endometrial carcinoma but rare in other common gynecological malignancies. Cancer Res 1997;57:3935-3940.

16.

16. Sakurada A , Suzuki A , Sato M , et al. Infrequent genetic alterations of the PTEN/MMAC1 gene in Japanese patients with primary cancers of the breast, lung, pancreas, kidney, and ovary. Jpn J Cancer Res 1997;88:1025-1028.

17.

17. Besson A , Robbins SM , Yong VW , PTEN/MMAC1/TEP1 in signal transduction and tumorigenesis. Eur J Biochem 1999;263:605-611.

18.

18. Khwaja A . Akt is more than just a bad kinase. Nature 1999;401:33-34.

19.

19. Haas-Kogan D , Shalev N , Wong M , Mills G , Yount G , Stokoe D . Protein kinase B (PKB/Akt) activity is elevated in glioblastoma cells due to mutations of the tumor suppressor PTEN/MMAC. Curr Biol 1998;8:1195-1198.

20.

20. DiCristofano A , Pesce B , Cordon-Cardo CA , Pandolfi PP . Pten is essential for embryonic development and tumor suppression. Nat Genet 1998;19:348-355.

21.

21. SuzuKI A , de la Pompa JL , Stambolic V , et al. High cancer susceptibility and embryonic lethality associated with mutation of the PTEN tumor suppressor gene in mice. Curr Biol 1998;8:1169-1178.

22.

22. Tonks NK , Neel BG . From form of function: Signaling by protein tyrosine phosphatases. Cell 1996;87:365-368.