title: Café-au-lait macules and pediatric malignancy caused by biallelic mutations in the DNA mismatch repair (MMR) gene PMS2.
abstract: A 14-year-old male presented with a T4 sigmoid adenocarcinoma, <10 colonic adenomas and multiple café-au-lait macules. Family history was not suggestive of a dominant hereditary form of colorectal cancer. Evaluation of the tumor revealed abnormal immunohistochemical staining of the PMS2 protein and high frequency microsatellite instability. Germline analysis identified biallelic PMS2 missense mutations. A new cancer syndrome caused by biallelic mutations in the mismatch repair genes, including PMS2, is now emerging and is characterized by café-au-lait macules, colonic polyps and a distinctive tumor spectrum.
authors.affiliation: Division of General Surgery, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada.
authors.forename: Carl-Christian
authors.initials: CC
authors.lastname: Jackson
authors.forename: Spring
authors.initials: S
authors.lastname: Holter
authors.forename: Aaron
authors.initials: A
authors.lastname: Pollett
authors.forename: Mark
authors.initials: M
authors.lastname: Clendenning
authors.forename: Shirley
authors.initials: S
authors.lastname: Chou
authors.forename: Leigha
authors.initials: L
authors.lastname: Senter
authors.forename: Raveena
authors.initials: R
authors.lastname: Ramphal
authors.forename: Steven
authors.initials: S
authors.lastname: Gallinger
authors.forename: Kym
authors.initials: K
authors.lastname: Boycott
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics*; D000293:Adolescent; D000483:Alleles; D019080:Cafe-au-Lait Spots / Q000150:complications / Q000235:genetics*; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000150:complications / Q000235:genetics*; D053843:DNA Mismatch Repair; D045643:DNA Repair Enzymes / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D000070976:Mismatch Repair Endonuclease PMS2; D020125:Mutation, Missense; D010375:Pedigree
chemical_list: D004268:DNA-Binding Proteins; D000251:Adenosine Triphosphatases; C094934:PMS2 protein, human; D000070976:Mismatch Repair Endonuclease PMS2; D045643:DNA Repair Enzymes