KAI1 metastasis suppressor protein in cervical cancer.

We are very pleased to hear of the molecular abnormalities in two new pancreatoblastomas of Kerr et al. In our recent study of nine pancreatoblastomas, allelic loss on chromosome 11p15.5 was present in 6 of 7 informative cases (86%), and mutations in the APC/ -catenin pathway in 6 of 9 cases (67%). These findings underscore the clinical association between pancreatoblastoma formation and Beckwith-Wiedemann syndrome, as well as a potential association of pancreatoblastoma with familial adenomatous polyposis (FAP). In the two additional pancreatoblastomas reported by Kerr et al, 11p15.5 allelic loss was found in both neoplasms, similar to the very high rate of 11p loss found in our series. In this regard, case 1 of Kerr et al is particularly exciting because this pancreatoblastoma showed selective loss of the maternal allele, something that we could not document in our pancreatoblastomas for which parental tissue was not available. This selective loss of the maternal 11p15.5 allele has been previously described in hepatoblastomas (neoplasms with clinical and genetic similarity to pancreatoblastomas), but not in pancreatoblastomas, and this strengthens the molecular link of pancreatoblastoma to BeckwithWiedemann syndrome. The finding of Kerr et al of an activating -catenin gene mutation in 1 of 2 pancreatoblastomas is also similar to our rate of -catenin mutations in 5 of 8 sporadic (non-FAP associated) pancreatoblastomas, and underscores the importance of alterations in the APC/ -catenin pathway in pancreatoblastoma development. It is certainly interesting to speculate what alternative molecular alterations in this pathway might be present in those cases that lack demonstrable -catenin mutations. As noted by Kerr et al, some possibilities would include inactivating APC or AXIN1 mutations. Our series included one patient with FAP whose pancreatoblastoma showed biallelic APC inactivation (a germ-line truncating mutation coupled with somatic 5q allelic loss) rather than -catenin mutation; we could not detect APC mutations in either of two sporadic pancreatoblastomas that were negative for -catenin mutations. However, it is certainly possible that the pancreatoblastoma in the Asian patient described by Kerr et al might show APC inactivation, since some hepatoblastomas in Asian, but not Western, patients have been shown to contain APC mutations. The 11 pancreatoblastomas which to date have been evaluated for molecular alterations in 11p and the APC/ -catenin pathway bear out two important points. First, the occasional occurrence of these tumors in patients with germ-line DNA abnormalities (in this case, BeckwithWiedemann syndrome and FAP) provides a clue to the genetic alterations in these tumors themselves. Second, the sporadic variants of these tumors will frequently harbor alterations in the same genes or in related genes of the same molecular pathway. Susan C. Abraham Ralph H. Hruban Johns Hopkins University School of Medicine Baltimore, Maryland