A novel germline POLE mutation causes an early onset cancer prone syndrome mimicking constitutional mismatch repair deficiency

AbstractIn a 14-year-old boy with polyposis and rectosigmoid carcinoma, we identified a novelPOLE germline mutation, p.(Val411Leu), previously found as recurrent somatic mutation in ‘ultramutated’ sporadic cancers. This is the youngest reported cancer patient with polymerase proofreading-associated polyposis indicating thatPOLE mutation p.(Val411Leu) may confer a more severe phenotype than previously reportedPOLE andPOLD1 germline mutations. The patient had multiple caf é-au-lait macules and a pilomatricoma mimicking the clinical phenotype of constitutional mismatch repair deficiency. We hypothesize that these skin features may be common to different types of constitutional DNA repair defects associated with polyposis and early-onset cancer.
Source: Familial Cancer - Category: Cancer & Oncology Source Type: research