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Cancer. 2016 Sep 15;122(18):2828-35. doi: 10.1002/cncr.30082. Epub 2016 May 31.

Increased incidence of FBXW7 and POLE proofreading domain mutations in young adult colorectal cancers.

Author information

1
Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
2
Department of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
3
Department of Surgery, Medical University of South Carolina, Charleston, South Carolina.
4
University of South Florida Morsani College of Medicine, Tampa, Florida.
5
Molecular Genomics Core Facility, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
6
Department of Sarcoma, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
7
Chemical Biology and Molecular Medicine, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
8
Adolescent and Young Adult Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
9
Department of Surgery, University of Tennessee Health Science Center, Memphis, Tennessee.

Abstract

BACKGROUND:

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.

METHODS:

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.

RESULTS:

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).

CONCLUSIONS:

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.

KEYWORDS:

F-box and WD repeat-containing protein 7 (FBXW7); adolescent and young adults; biomarkers; colorectal cancer

PMID:
27244218
PMCID:
PMC5014625
DOI:
10.1002/cncr.30082
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

Disclosures: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr. Teer reports personal fees from Philips, outside the submitted work. In addition, Dr. Teer has a patent pending for a large data storage model. The other authors have nothing to disclose.

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