A de novo MLH1 germ line mutation in a 31-year-old colorectal cancer patient.
Hereditary nonpolyposis colorectal cancer is an autosomal dominant cancer predisposition syndrome caused by inherited germ line mutations in DNA mismatch repair genes, predominantly MSH2 and MLH1. Here we report the first proven de novo germ line mutation in MLH1 (c.666dupA) identified in a 31-year-old colorectal cancer patient with the alteration being present in a heterozygous state in all three germ layers and homozygously in his colon cancer. The mutation was absent in both biological parents and all sibs available. Despite extensive polymorphic marker analysis, the parental origin of c.666dupA could not be conclusively determined, representing either a single mutational event in a parental germ cell or (maternal) gonadal mosaicism. Although rare, consequential application of the Bethesda guidelines for genetic testing should allow the clinician to readily identify colorectal cancer patients below age 50 years who carry de novo mismatch repair gene mutations.
Plasilova
Martina
M
Research Group Human Genetics, Division of Medical Genetics UKBB, Center of Biomedicine DKBW, University of Basel, Basel, Switzerland.
Zhang
Jian
J
Okhowat
Roberta
R
Marra
Giancarlo
G
Mettler
Markus
M
Mueller
Hansjakob
H
Heinimann
Karl
K
D048868:Adaptor Proteins, Signal Transducing; D000230:Adenocarcinoma / Q000235:genetics*; D000328:Adult; D002352:Carrier Proteins / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics*; D005190:Family; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D009687:Nuclear Proteins / Q000235:genetics*
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D000070957:MutL Protein Homolog 1