title: Increased incidence of FBXW7 and POLE proofreading domain mutations in young adult colorectal cancers.
abstract: The incidence and outcomes of patients with colorectal cancer (CRC) varies by age. Younger patients tend to have sporadic cancers that are not detected by screening and worse survival. To understand whether genetic differences exist between age cohorts, the authors sought to characterize unique genetic alterations in patients with CRC.
  
  
  
  In total, 283 patients who were diagnosed with sporadic CRC between 1998 and 2010 were identified and divided by age into 2 cohorts-ages ≤45 years (the younger cohort) and ≥65 years (the older cohort)-and targeted exome sequencing was performed. The Fisher exact test was used to detect differences in mutation frequencies between the 2 groups. Whole exome sequencing was performed on 21 additional younger patient samples for validation. Findings were confirmed in The Cancer Genome Atlas CRC data set.
  
  
  
  In total, 246 samples were included for final analysis (195 from the older cohort and 51 from the younger cohort). Mutations in the FBXW7 gene were more common in the younger cohort (27.5% vs 9.7%; P = .0022) as were mutations in the proofreading domain of polymerase ε catalytic subunit (POLE) (9.8% vs 1%; P = .0048). There were similar mutation rates between cohorts with regard to TP53 (64.7% vs 61.5%), KRAS (43.1% vs 46.2%), and APC (60.8% vs 73.8%). BRAF mutations were numerically more common in the older cohort, although the difference did not reach statistical significance (2% vs 9.7%; P = .082).
  
  
  
  In this retrospective study, a unique genetic profile was identified for younger patients who have CRC compared with patients who are diagnosed at an older age. These findings should be validated in a larger study and could have an impact on future screening and treatment modalities for younger patients with CRC. Cancer 2016. © 2016 American Cancer Society. Cancer 2016;122:2828-2835. © 2016 American Cancer Society.
authors.affiliation: Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors.forename: Nishi
authors.initials: N
authors.lastname: Kothari
authors.affiliation: Department of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors.forename: Jamie K
authors.initials: JK
authors.lastname: Teer
authors.affiliation: Department of Surgery, Medical University of South Carolina, Charleston, South Carolina.
authors.forename: Andrea M
authors.initials: AM
authors.lastname: Abbott
authors.affiliation: University of South Florida Morsani College of Medicine, Tampa, Florida.
authors.forename: Thejal
authors.initials: T
authors.lastname: Srikumar
authors.affiliation: Department of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Molecular Genomics Core Facility, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors.forename: Sean J
authors.initials: SJ
authors.lastname: Yoder
authors.affiliation: Department of Sarcoma, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.|Chemical Biology and Molecular Medicine, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Brohl
authors.affiliation: Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Kim
authors.affiliation: Department of Sarcoma, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.|Adolescent and Young Adult Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.|Chemical Biology and Molecular Medicine, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors.forename: Damon R
authors.identifier: 0000-0002-8238-2465
authors.initials: DR
authors.lastname: Reed
authors.affiliation: Department of Surgery, University of Tennessee Health Science Center, Memphis, Tennessee.
authors.forename: David
authors.initials: D
authors.lastname: Shibata
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D004257:DNA Polymerase II / Q000235:genetics* / Q000378:metabolism; D044783:F-Box Proteins / Q000235:genetics* / Q000378:metabolism; D000073979:F-Box-WD Repeat-Containing Protein 7; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009154:Mutation; D000075223:Poly-ADP-Ribose Binding Proteins; D012189:Retrospective Studies; D044767:Ubiquitin-Protein Ligases / Q000235:genetics* / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D044783:F-Box Proteins; D000073979:F-Box-WD Repeat-Containing Protein 7; C513273:FBXW7 protein, human; D000075223:Poly-ADP-Ribose Binding Proteins; D044767:Ubiquitin-Protein Ligases; D004257:DNA Polymerase II; C119525:POLE protein, human
keywords: F-box and WD repeat-containing protein 7 (FBXW7); adolescent and young adults; biomarkers; colorectal cancer