A Novel Phosphatase Gene on 10q23, MINPP, in Hereditary and Sporadic Breast Cancer
Abstract
PTEN is a tumor suppressor gene on 10q23 and encodes a dual specificity phosphatase. One of the major substrates for PTEN is phosphotidylinositol (3,4,5) triphosphate in the P13 kinase pathway. When PTEN is dysfunctional or absent, P-Akt is high and hence, anti-apoptotic. PTEN is a major susceptibility gene for Cowden syndrome (CS), a hereditary disorder with a high risk of breast and thyroid cancer, and appears to be involved in a broad range of tumors. In addition, germline PTENmutations have been found in a developmental disorder, Bannayan-Riley-Ruvalcaba syndrome (ERR) as well. Previously not thought to be associated with cancer risk, ERR families and cases with germline PTEN mutations have recently been shown to be at risk for cancers and especially breast tumors. Between 10-80% (mean 60%) of CS families and 60% of ERR individuals have germline PTENmutations. Families that do not have germline PTEN mutations are not inconsistent with linkage to the l0q22-23 region. Thus, genes with related function to PTEN in the lOq2l-q25 region are good candidates genes for PTENmutation negative CS, ERR and related sporadic tumors, eg, those of the breast and thyroid. MINPP1 lies no more than 1 Mb upstream of PTEN and encodes an inositol polyphosphate phosphatase. while we have found no intragenic germline MINPPl mutation in CS and ERR, MINPPl has been found to be co-deleted with PTEN in one case of ERR with prominent GI features. MINPPl also appears to act as a low penetrance susceptibility gene for sporadic follicular thyroid neoplasia but not breast cancer. While no somatic intragenic MINPP1 mutations were found in whole breast cancers, co-deletion of PTEN and MINPPl occur in 3040% of sporadic breast carcinomas. More interestingly, these codeletions have been shown to occur in the stroma. Therefore, MINPPl plays a comodulatory (non-traditional) role in hereditary and sporadic breast cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2003
- Accession Number
- ADA420336
Entities
People
- Charis Eng
Organizations
- Ohio State University