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

作者：Wimmer Katharina^*; Beilken Andreas; Nustede Rainer; Ripperger Tim; Lamottke Britta; Ure Benno; Steinmann Diana; Reineke Plaass Tanja; Lehmann Ulrich; Zschocke Johannes; Valle Laura; Fauth Christine; Kratz Christian P

来源：Familial Cancer, 2017, 16(1): 67-71.

DOI：10.1007/s10689-016-9925-1

• Polymerase proofreading-associated polyposis
• Constitutional mismatch repair deficiency
• Cafe-au-lait macule
• Pilomatricoma
• Colon cancer

In a 14-year-old boy with polyposis and rectosigmoid carcinoma, we identified a novel POLE 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 that POLE mutation p.(Val411Leu) may confer a more severe phenotype than previously reported POLE and POLD1 germline mutations. The patient had multiple caf,-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.

• 出版日期2017-1