In preliminary screens, mutations of PTEN were detected in 31% (13/42) of glioblastoma cell lines and xenografts, 100% (4/4) of prostate cancer cell lines, 6% (4/65) of breast cancer cell lines and xenografts, and 17% (3/18) of primary glioblastomas.
These data indicate that somatic mutations of PTEN/ MMAC1 occur in only a small fraction of primary breast cancers and confirm the role of this gene in the etiology of Cowden disease.
Germ-line PTEN mutations were detected in all of five families with both breast cancer and CD, in one family with juvenile polyposis syndrome, and in one of four families with breast and thyroid tumors.
Most recently, a putative tumor suppressor gene (PTEN/MMAC1) has been identified in the region between D10S215 and an adjacent, more telomeric marker (D10S541) and was found to be altered in breast cancers, prostate cancers, and glioblastomas.
A new tumor suppressor gene PTEN/MMAC1 was recently isolated at chromosome 10q23 and found to be inactivated by point mutation or homozygous deletion in glioma, prostate and breast cancer.
The tumor cell line is marked by multiple additional genetic changes including a high degree of aneuploidy, an acquired mutation of TP53 with wild-type allele loss, an acquired homozygous deletion of the PTEN gene, and loss of heterozygosity at multiple loci known to be involved in the pathogenesis of breast cancer.
While preliminary, these findings suggest that further study is warranted to determine whether this allelic variant of PTEN could function as a low penetrance breast cancer susceptibility allele.
Therefore, PTEN germline mutations were searched for in a series of 20 unrelated women with breast cancer who also had a personal or familial breast-brain tumour history.
A novel tumor suppressor gene, PTEN, has recently been identified at chromosome 10q23, which is inactivated in a number of different tumor types including breast cancer.
To further determine the role of PTEN/MMAC1 in breast cancer in Chinese, we used loss of heterozygosity (LOH), single strand conformation polymorphism (SSCP) with direct sequencing of variant bands, and Southern blot analysis methods to analyze mutations in PTEN/MMAC1 in 52 cases of breast cancer.None had LOH at chromosome 10q23.3.
PTEN coordinates G(1) arrest by down-regulating cyclin D1 via its protein phosphatase activity and up-regulating p27 via its lipid phosphatase activity in a breast cancer model.
Germ-line mutations in the PTEN tumor suppressor gene are causative of Cowden's breast cancer predisposition syndrome, and PTEN is frequently mutated in sporadic breast cancers.