Genetic and epigenetic alterations of the PTEN gene in soft tissue sarcomas

Ken Ichi Kawaguchi, Yoshinao Oda, Tsuyoshi Saito, Tomonari Takahira, Hidetaka Yamamoto, Sadafumi Tamiya, Yukihide Iwamoto, Masazumi Tsuneyoshi

Research output: Contribution to journalArticle

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Abstract

The PTEN/MMAC1 (PTEN) gene was identified as a tumor suppressor gene encoding a cytoplasmic protein that controls cellular processes. To investigate the potential role and the alteration of the PTEN gene in soft tissue sarcomas (STSs), we searched for homozygous deletion and promoter hypermethylation in a series of 48 STSs that was composed of malignant fibrous histiocytoma, leiomyosarcoma, malignant peripheral nerve sheath tumor, including 2 cases with a mutation that we previously reported; differential polymerase chain reaction and methylation-specific polymerase chain reaction, respectively, were used for the analyses. Furthermore, to determine whether PTEN gene alterations are involved in the down-regulation of PTEN expression, we examined the expression of PTEN protein in 38 cases in which paraffin-embedded tissues were available for immunohistochemical analysis. In addition to our previous results showing that 2 (4%) of 51 cases had a PTEN mutation, promoter methylation was recognized in 6 (13%) of 48 cases, and homozygous deletion was detected in 1 (2%) of 48 cases in the current study. Of 6 cases with promoter methylation of PTEN gene, 5 were malignant peripheral nerve sheath tumor. Decreased expression of PTEN protein was recognized in 11 (29%) of 38 STS cases. Of 9 cases with PTEN alterations (6 cases with promoter methylation, 2 with mutation, and 1 with homozygous deletion), 3 (33%) showed decreased expression of PTEN protein. Furthermore, decreased expression of the PTEN gene showed a statistically significant correlation with high MIB-1 labeling index in 38 STS cases examined (P = .0441). In conclusion, promoter methylation and homozygous deletion of the PTEN gene were found to be relatively rare events in cases of STS, as is mutation of the gene. Of 9 cases with a PTEN alteration, 3 (33%) showed a decrease in PTEN expression, indicating that PTEN gene alterations seem to play a minor role in the inactivation of PTEN in these tumors. Furthermore, although a further detailed analysis of a larger number of cases is still necessary, the present results suggest that PTEN expression may be a useful indicator of cell proliferation in patients with STS.

Original languageEnglish
Pages (from-to)357-363
Number of pages7
JournalHuman Pathology
Volume36
Issue number4
DOIs
Publication statusPublished - Apr 2005

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Epigenomics
Sarcoma
Methylation
PTEN Phosphohydrolase
Genes
Mutation
Neurilemmoma
Malignant Fibrous Histiocytoma
Polymerase Chain Reaction
Leiomyosarcoma
Gene Deletion
Tumor Suppressor Genes
Paraffin
Down-Regulation
Cell Proliferation
Gene Expression
Neoplasms
Proteins

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

Cite this

Genetic and epigenetic alterations of the PTEN gene in soft tissue sarcomas. / Kawaguchi, Ken Ichi; Oda, Yoshinao; Saito, Tsuyoshi; Takahira, Tomonari; Yamamoto, Hidetaka; Tamiya, Sadafumi; Iwamoto, Yukihide; Tsuneyoshi, Masazumi.

In: Human Pathology, Vol. 36, No. 4, 04.2005, p. 357-363.

Research output: Contribution to journalArticle

Kawaguchi, Ken Ichi ; Oda, Yoshinao ; Saito, Tsuyoshi ; Takahira, Tomonari ; Yamamoto, Hidetaka ; Tamiya, Sadafumi ; Iwamoto, Yukihide ; Tsuneyoshi, Masazumi. / Genetic and epigenetic alterations of the PTEN gene in soft tissue sarcomas. In: Human Pathology. 2005 ; Vol. 36, No. 4. pp. 357-363.
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abstract = "The PTEN/MMAC1 (PTEN) gene was identified as a tumor suppressor gene encoding a cytoplasmic protein that controls cellular processes. To investigate the potential role and the alteration of the PTEN gene in soft tissue sarcomas (STSs), we searched for homozygous deletion and promoter hypermethylation in a series of 48 STSs that was composed of malignant fibrous histiocytoma, leiomyosarcoma, malignant peripheral nerve sheath tumor, including 2 cases with a mutation that we previously reported; differential polymerase chain reaction and methylation-specific polymerase chain reaction, respectively, were used for the analyses. Furthermore, to determine whether PTEN gene alterations are involved in the down-regulation of PTEN expression, we examined the expression of PTEN protein in 38 cases in which paraffin-embedded tissues were available for immunohistochemical analysis. In addition to our previous results showing that 2 (4{\%}) of 51 cases had a PTEN mutation, promoter methylation was recognized in 6 (13{\%}) of 48 cases, and homozygous deletion was detected in 1 (2{\%}) of 48 cases in the current study. Of 6 cases with promoter methylation of PTEN gene, 5 were malignant peripheral nerve sheath tumor. Decreased expression of PTEN protein was recognized in 11 (29{\%}) of 38 STS cases. Of 9 cases with PTEN alterations (6 cases with promoter methylation, 2 with mutation, and 1 with homozygous deletion), 3 (33{\%}) showed decreased expression of PTEN protein. Furthermore, decreased expression of the PTEN gene showed a statistically significant correlation with high MIB-1 labeling index in 38 STS cases examined (P = .0441). In conclusion, promoter methylation and homozygous deletion of the PTEN gene were found to be relatively rare events in cases of STS, as is mutation of the gene. Of 9 cases with a PTEN alteration, 3 (33{\%}) showed a decrease in PTEN expression, indicating that PTEN gene alterations seem to play a minor role in the inactivation of PTEN in these tumors. Furthermore, although a further detailed analysis of a larger number of cases is still necessary, the present results suggest that PTEN expression may be a useful indicator of cell proliferation in patients with STS.",
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AU - Yamamoto, Hidetaka

AU - Tamiya, Sadafumi

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