[HTML][HTML] Epithelial-specific loss of PTEN results in colorectal juvenile polyp formation and invasive cancer

VM Durban, M Jansen, EJ Davies, FH Morsink… - The American Journal of …, 2014 - Elsevier
VM Durban, M Jansen, EJ Davies, FH Morsink, GJA Offerhaus, AR Clarke
The American Journal of Pathology, 2014Elsevier
Cowden syndrome (CS) is a rare autosomal dominant cancer-prone disorder caused by
germ-line mutation of the phosphatase and tensin homolog mutated on chromosome 10
(PTEN) tumor-suppressor gene. Affected patients commonly develop juvenile polyps, and
show an elevated risk of developing colorectal cancers. The etiology of these peculiar
polyps remains unclear, although previous work has suggested somatic PTEN alterations in
the stroma of juvenile polyps. After a long latency period, we find epithelial-specific PTEN …
Cowden syndrome (CS) is a rare autosomal dominant cancer-prone disorder caused by germ-line mutation of the phosphatase and tensin homolog mutated on chromosome 10 (PTEN) tumor-suppressor gene. Affected patients commonly develop juvenile polyps, and show an elevated risk of developing colorectal cancers. The etiology of these peculiar polyps remains unclear, although previous work has suggested somatic PTEN alterations in the stroma of juvenile polyps. After a long latency period, we find epithelial-specific PTEN deletion to cause formation of juvenile polyps in the colorectum without stromal PTEN loss. More important, we find that these lesions closely recapitulate all of the characteristic histopathological features of juvenile polyps seen in patients with CS, including stromal alterations and dysplastic transformation to colorectal carcinoma. The stromal alterations we identify after epithelial-specific PTEN loss suggest that PTEN may be involved in altered epithelial-mesenchymal cross talk, which, in turn, predisposes to colorectal neoplasia and polyposis. Our transgenic model is the first to recapitulate colorectal juvenile polyposis in patients with CS. We conclude that stromal PTEN loss is not a prerequisite for the formation of juvenile polyps, and that colorectal juvenile polyps in CS are bona fide neoplastic precursor lesions.
Elsevier