Comprehensive genomic landscapes in early and later onset colorectal cancer

Christopher H. Lieu, Erica A. Golemis, Ilya G. Serebriiskii, Justin Newberg, Amanda Hemmerich, Caitlin Connelly, Wells A. Messersmith, Cathy Eng, S Gail Eckhardt, Garrett Frampton, Matthew Cooke, Joshua E. Meyer

Research output: Contribution to journalArticle

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Abstract

Purpose: The incidence rates of colorectal cancers are increasing in young adults. The objective of this study was to investigate genomic differences between tumor samples collected from younger and older patients with colorectal cancer. Experimental Design: DNA was extracted from 18,218 clinical specimens, followed by hybridization capture of 3,769 exons from 403 cancer-related genes and 47 introns of 19 genes commonly rearranged in cancer. Genomic alterations (GA) were determined, and association with patient age and microsatellite stable/microsatellite instability high (MSS/MSI-H) status established. Results: Overall genomic alteration rates in the younger (<40) and older (>50) cohorts were similar in the majority of the genes analyzed. Gene alteration rates in the microsatellite stable (MSS) younger and older cohorts were largely similar, with several notable differences. In particular, TP53 (FDR < 0.01) and CTNNB1 (FDR ¼ 0.01) alterations were more common in younger patients with colorectal cancer, and APC (FDR < 0.01), KRAS (FDR < 0.01), BRAF (FDR < 0.01), and FAM123B (FDR < 0.01) were more commonly altered in older patients with colorectal cancer. In the MSI-H cohort, the majority of genes showed similar rate of alterations in all age groups, but with significant differences seen in APC (FDR < 0.01), BRAF (FDR < 0.01), and KRAS (FDR < 0.01). Conclusions: Tumors from younger and older patients with colorectal cancer demonstrated similar overall rates of genomic alteration. However, differences were noted in several genes relevant to biology and response to therapy. Further study will need to be conducted to determine whether the differences in gene alteration rates can be leveraged to provide personalized therapies for young patients with early-onset sporadic colorectal cancer.

Original languageEnglish (US)
Pages (from-to)5852-5858
Number of pages7
JournalClinical Cancer Research
Volume25
Issue number19
DOIs
StatePublished - Oct 1 2019

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Colorectal Neoplasms
Genes
Microsatellite Repeats
Neoplasms
Microsatellite Instability
Neoplasm Genes
Introns
Young Adult
Exons
Research Design
Age Groups
DNA
Incidence
Therapeutics

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Lieu, C. H., Golemis, E. A., Serebriiskii, I. G., Newberg, J., Hemmerich, A., Connelly, C., ... Meyer, J. E. (2019). Comprehensive genomic landscapes in early and later onset colorectal cancer. Clinical Cancer Research, 25(19), 5852-5858. https://doi.org/10.1158/1078-0432.CCR-19-0899

Comprehensive genomic landscapes in early and later onset colorectal cancer. / Lieu, Christopher H.; Golemis, Erica A.; Serebriiskii, Ilya G.; Newberg, Justin; Hemmerich, Amanda; Connelly, Caitlin; Messersmith, Wells A.; Eng, Cathy; Eckhardt, S Gail; Frampton, Garrett; Cooke, Matthew; Meyer, Joshua E.

In: Clinical Cancer Research, Vol. 25, No. 19, 01.10.2019, p. 5852-5858.

Research output: Contribution to journalArticle

Lieu, CH, Golemis, EA, Serebriiskii, IG, Newberg, J, Hemmerich, A, Connelly, C, Messersmith, WA, Eng, C, Eckhardt, SG, Frampton, G, Cooke, M & Meyer, JE 2019, 'Comprehensive genomic landscapes in early and later onset colorectal cancer', Clinical Cancer Research, vol. 25, no. 19, pp. 5852-5858. https://doi.org/10.1158/1078-0432.CCR-19-0899
Lieu CH, Golemis EA, Serebriiskii IG, Newberg J, Hemmerich A, Connelly C et al. Comprehensive genomic landscapes in early and later onset colorectal cancer. Clinical Cancer Research. 2019 Oct 1;25(19):5852-5858. https://doi.org/10.1158/1078-0432.CCR-19-0899
Lieu, Christopher H. ; Golemis, Erica A. ; Serebriiskii, Ilya G. ; Newberg, Justin ; Hemmerich, Amanda ; Connelly, Caitlin ; Messersmith, Wells A. ; Eng, Cathy ; Eckhardt, S Gail ; Frampton, Garrett ; Cooke, Matthew ; Meyer, Joshua E. / Comprehensive genomic landscapes in early and later onset colorectal cancer. In: Clinical Cancer Research. 2019 ; Vol. 25, No. 19. pp. 5852-5858.
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AU - Connelly, Caitlin

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