Various genes have been identified to play a role in the pathogenesis of 
follicular thyroid tumors. Cowden syndrome is the only known familial syndrome 
with an increased risk of both follicular thyroid adenoma (FA) and carcinoma 
(FTC). Germline mutations in the tumor suppressor gene PTEN, which encodes a 
dual-specificity phosphatase, have been found in up to 80% of patients with 
Cowden syndrome suggesting a role of PTEN in the pathogenesis of follicular 
thyroid tumors. Although somatic intragenic mutations in PTEN, which maps to 
10q23.3, are rarely found in follicular tumors, loss of heterozygosity (LOH) of 
markers within 10q22-24 occurs in about 25%. Recently, another phosphatase gene, 
MINPP1, has been localized to 10q23.3. MINPP1 has the ability to remove 
3-phosphate from inositol phosphate substrates, a function that overlaps that of 
PTEN. Because of this overlapping function with PTEN and the physical location 
of MINPP1 to a region with frequent LOH in follicular thyroid tumors, we 
considered it to be an excellent candidate gene that could contribute to the 
pathogenesis of follicular thyroid tumors. We analyzed DNA from tumor and 
corresponding normal tissue from 23 patients with FA and 15 patients with FTC 
for LOH and mutations at the MINPP1 locus. LOH was identified in four malignant 
and three benign tumors. One of these FTCs with LOH was found to harbor a 
somatic c.122C > T or S41L mutation. We also found two germline sequence 
variants, c.809A > G (Q270R) and IVS3 + 34T > A. The c.809A > G variant was 
found in only one patient with FA but not in patients with FTC or normal 
controls. More interestingly, IVS3 + 34T > A was found in about 15% of FA cases 
and normal controls but not in patients with FTC. These results suggest a role 
for MINPP1 in the pathogenesis of at least a subset of malignant follicular 
thyroid tumors, and MINPP1 might act as a low penetrance predisposition allele 
for FTC.