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 PI3 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 PTEN mutations have been found in a developmental disorder, Bannayan-Riley-Ruvalcaba syndrome (BRR) as well. This is an autosomal dominant disorder characterised by macrocephaly, lipomatosis, hemangiomatosis and speckled penis. Previously not thought to be associated with cancer risk, BRR 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 BRR individuals have germline PTENmutations. Families that do not have germline PTEN mutations are not inconsistent with linkage to the 10q22-23 region. Thus, genes with related function to PTEN in the 10q21-q25 region are good candidates genes for PTEN mutation negative CS, BRR and related sporadic tumors, eg, those of the breast and thyroid. MINPPI lies no more than 1 Mb upstream of PTEN and encodes an inositol polyphosphate phosphatase. In Year 1 of this award, the PI has ascertained 14 unrelated CS probands, 22 BRR probands and 20 CS-like probands known not to harbor germline PTEN mutations. To date, they have not been found to carry germline MINPPI mutations. We found 4 malignant and 3 benign thyroid tumors to harbor deletion or intragenic mutation of MINPPI. More interestingly, IVS3+34T>A was found in about 15% of FA cases and normal controls but not in patients with FTC.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2001
- Accession Number
- ADA396894
Entities
People
- Charis Eng
Organizations
- Ohio State University