Neoplasia is associated with a number of genetic alterations. One of these alterations has been localized to the chromosome 10q23. In the March 28, 1997 issue of Science, Li et al describe a protein which is mutated in a number of human cancers including those from breast, brain and prostate. This protein interacts with actin filaments and is a putative protein tyrosine phosphatase. Li et al have called this protein PTEN (phosphatase and tensin homolog deleted on chromosome 10). Steck et al ,who simulatenously located the same gene have adopted the name, MMAC1 (mutated in multiple advance cancers 1). The 5.5-kb mRNA of the PTEN/MMAC1 is widely expressed in human tissues and it appears to have alternately spliced variants. The N-terminal domain of the gene codes for a 403-amino acid protein that is likely a protein phosphatase and is related to the CDC14 which is an enzyme that controls the cell division.

In human tumor cell lines, and xenografts, a number of mutations were commonly found in the PTEN/MMAC1 (Table 1-2). These mutations led to a number of frameshifts, stop codon, in-frameshift, and change of Gly to Arg or Met to Leu (Table 1). These mutations were also present in primary human tumors from brain (glioblastoma multiforme), as well as breast and prostate carcinomas. Mutational analysis of PTEN in CD kindreds identified germline mutations in four of five families. Both nonsense and missense mutations were present that predict disruption of the protein tyrosine/dual-specificity phosphatase domain of this gene. Thus, PTEN/MMAC1 appears to be a tumor suppressor gene in the germline.

FIGURE LEGENDS (from the top)

Figure 1. Mammographic image of breast cancer. Breast cancer appears as a dense area within the mammogram.

Figure 2. Gross appearance of breast cancer. Breast cancer appears as a stellate, hard tumor which infiltrates the surrounding breast tissue.

Arch, E. M.; Goodman, B. K.; Van Wesep, R. A.; McKusick, V. A.; Geraghty, M. T. : Deletion of PTEN in a patient with Bannayan-Riley-Ruvalcaba (BRR) syndrome suggests allelism with Cowden disease. Submitted , 1997.

Li, J.; Yen, C.; Liaw, D.; Podsypanina, K.; Bose, S.; Wang, S. I.; Puc, J.; Miliaresis, C.; Rodgers, L.; McCombie, R.; Bigner, S. H.; Giovanella, B. C.; Ittmann, M.; Tycko, B.; Hibshoosh, H.; Wigler, M. H.; Parsons, R. : PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science 275: 1943-1946, 1997

Liaw, D.; Marsh, D. J.; Li, J.; Dahia, P. L. M.; Wang, S. I.; Zheng, Z.; Bose, S.; Call, K. M.; Tsou, H. C.; Peacocke, M.; Eng, C.; Parsons, R. : Germline mutations of the PTEN gene in Cowden disease, an inherited breast and thyroid cancer syndrome.Nature Genet. 16: 64-67, 1997.

Steck, P. A.; Pershouse, M. A.; Jasser, S. A.; Yung, W. K. A.; Lin, H.; Ligon, A. H.; Langford, L. A.; Baumgard, M. L.; Hattier, T.; Davis, T.; Frye, C.; Hu, R.; Swedlund, B.; Teng, D. H. F.; Tavtigian, S. V. : Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers.Nature Genet. 15: 356-362, 1997.

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