Fanconi anemia gene mutations in young-onset pancreatic cancer.
Genes of the Fanconi complementation groups [Fanconi anemia (FA) genes] are suggested to be involved in homologous DNA recombination and produce FA when two allelic mutations are inherited. BRCA2 is an FA gene and additionally conveys an inherited risk for breast, ovarian, and pancreatic cancer for individuals carrying a single mutated allele [N. G. Howlett et al., Science (Wash. DC), 297: 606-609, 2002]. Here we report inherited and somatic mutations of FANCC and FANCG present in young-onset pancreatic cancer. This may imply a general involvement of Fanconi genes with an inherited risk of cancer. The known hypersensitivity of Fanconi cells to mitomycin and other therapeutic agents [M. S. Sasaki, Nature (Lond.), 257: 501-503, 1975] suggests a therapeutic utility for a more complete characterization of the DNA repair defects and their causative genetic mutations in pancreatic cancer.
Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland 21231, USA.
Michiel S
MS
van der Heijden
Charles J
CJ
Yeo
Ralph H
RH
Hruban
Scott E
SE
Kern
D000367:Age Factors; D000483:Alleles; D000818:Animals; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics*; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins / Q000235:genetics*; D052218:Fanconi Anemia Complementation Group C Protein; D052241:Fanconi Anemia Complementation Group G Protein; D051856:Fanconi Anemia Complementation Group Proteins; D020868:Gene Silencing; D020022:Genetic Predisposition to Disease; D006801:Humans; D019656:Loss of Heterozygosity; D051379:Mice; D009154:Mutation; D009368:Neoplasm Transplantation; D009687:Nuclear Proteins; D010190:Pancreatic Neoplasms / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D014183:Transplantation, Heterologous
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C497651:FANCC protein, human; C499909:FANCG protein, human; C497652:Fancc protein, mouse; C499910:Fancg protein, mouse; D052218:Fanconi Anemia Complementation Group C Protein; D052241:Fanconi Anemia Complementation Group G Protein; D051856:Fanconi Anemia Complementation Group Proteins; D009687:Nuclear Proteins; D011506:Proteins