title: A novel germline POLE mutation causes an early onset cancer prone syndrome mimicking constitutional mismatch repair deficiency.
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.
authors: Division of Human Genetics, Medical University Innsbruck, Peter-Mayr-Straße 1, 6020, Innsbruck, Austria. katharina.wimmer@i-med.ac.at.
authors: Katharina
authors: K
authors: Wimmer
authors: Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany.
authors: Andreas
authors: A
authors: Beilken
authors: Department of Surgery, Children's Hospital, Hannover Medical School, Hannover, Germany.
authors: Rainer
authors: R
authors: Nustede
authors: Institute of Human Genetics, Hannover Medical School, Hannover, Germany.
authors: Tim
authors: T
authors: Ripperger
authors: Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany.
authors: Britta
authors: B
authors: Lamottke
authors: Department of Surgery, Children's Hospital, Hannover Medical School, Hannover, Germany.
authors: Benno
authors: B
authors: Ure
authors: Department of Radiotherapy and Special Oncology, Hannover Medical School, Hannover, Germany.
authors: Diana
authors: D
authors: Steinmann
authors: Institute of Pathology, Hannover Medical School, Hannover, Germany.
authors: Tanja
authors: T
authors: Reineke-Plaass
authors: Institute of Pathology, Hannover Medical School, Hannover, Germany.
authors: Ulrich
authors: U
authors: Lehmann
authors: Division of Human Genetics, Medical University Innsbruck, Peter-Mayr-Straße 1, 6020, Innsbruck, Austria.
authors: Johannes
authors: J
authors: Zschocke
authors: Hereditary Cancer Program, Catalan Institute of Oncology, IDIBELL, Hospitalet De Llobregat, Spain.
authors: Laura
authors: L
authors: Valle
authors: Division of Human Genetics, Medical University Innsbruck, Peter-Mayr-Straße 1, 6020, Innsbruck, Austria.
authors: Christine
authors: C
authors: Fauth
authors: Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany.
authors: Christian P
authors: CP
authors: Kratz
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D001932:Brain Neoplasms / Q000235:genetics*; D019080:Cafe-au-Lait Spots / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics*; D004257:DNA Polymerase II / Q000235:genetics*; D018095:Germ-Line Mutation; D006201:Hair Diseases / Q000235:genetics; D006801:Humans; D008297:Male; D053842:Microsatellite Instability; D009386:Neoplastic Syndromes, Hereditary / Q000235:genetics*; D018296:Pilomatrixoma / Q000235:genetics; D000075223:Poly-ADP-Ribose Binding Proteins; D012878:Skin Neoplasms / Q000235:genetics
chemical_list: D000075223:Poly-ADP-Ribose Binding Proteins; D004257:DNA Polymerase II; C119525:POLE protein, human
keywords: Café-au-lait macule; Colon cancer; Constitutional mismatch repair deficiency; Pilomatricoma; Polymerase proofreading-associated polyposis