2. Academic Validation
  3. A novel germline POLE mutation causes an early onset cancer prone syndrome mimicking constitutional mismatch repair deficiency

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

  • Fam Cancer. 2017 Jan;16(1):67-71. doi: 10.1007/s10689-016-9925-1.
Katharina Wimmer 1,  Andreas Beilken 2,  Rainer Nustede 3,  Tim Ripperger 4,  Britta Lamottke 2,  Benno Ure 3,  Diana Steinmann 5,  Tanja Reineke-Plaass 6,  Ulrich Lehmann 6,  Johannes Zschocke 7,  Laura Valle 8,  Christine Fauth 7,  Christian P Kratz 2
Affiliations

Affiliations

  • 1 Division of Human Genetics, Medical University Innsbruck, Peter-Mayr-Straße 1, 6020, Innsbruck, Austria. [email protected].
  • 2 Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany.
  • 3 Department of Surgery, Children's Hospital, Hannover Medical School, Hannover, Germany.
  • 4 Institute of Human Genetics, Hannover Medical School, Hannover, Germany.
  • 5 Department of Radiotherapy and Special Oncology, Hannover Medical School, Hannover, Germany.
  • 6 Institute of Pathology, Hannover Medical School, Hannover, Germany.
  • 7 Division of Human Genetics, Medical University Innsbruck, Peter-Mayr-Straße 1, 6020, Innsbruck, Austria.
  • 8 Hereditary Cancer Program, Catalan Institute of Oncology, IDIBELL, Hospitalet De Llobregat, Spain.
PMID: 27573199 DOI: 10.1007/s10689-016-9925-1
Abstract

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 café-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.

Keywords

Café-au-lait macule; Colon cancer; Constitutional mismatch repair deficiency; Pilomatricoma; Polymerase proofreading-associated polyposis.

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