LAUSR

The comprehensive genomic analysis by Next generation sequencing can make us find many oncodriver gene mutations. And at the same time, we can find many gene structural mutations outside of oncodriver gene mutations. Most of such gene mutations are not identified about the pathologic significance, so that they are called variants of uncertain significant (VUS) gene mutations. And evaluations of their function are important for patient treatment. Recently, we had experienced an adult pancreatoblastoma case. Using commercially available the cancer panel, OncoDeep, we found a missense mutation in APC gene, which has not been reported in the UMD-APC mutations database. Immunohistochemically analysis revealed nuclear accumulation of the b-catenin protein. Because CTNNB1 was not mutated in this case, these results indicated that the missense mutation of APC lost its function and caused Wnt signal activation. To identify the structure mutation of APC gene in germ line, we have done target sequence of DNA extracted from oral mucosa. We found heterozygous of APC gene. It was assumed that loss of heterozygosis of APC gene causes Wnt signal activation in pancreatoblastoma cells in this case. The patient harboring pathological APC gene mutations in germ line generally develop colon polyposis, but this patient did not have the past history of colon polyposis. To make clear the APC mutation we found in this case causes functional loss, we have done functional assay with cell line model. The results indicated the APC gene mutation in this case causes partial loss of suppression of Wnt signal activation. This is a very important case report in NGS era in which we found many VUS gene mutations. We will present detail analyzed data together with clinical course.