Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Enhancing the Landscape of Colorectal Cancer Using Targeted Deep Sequencing

Version 1 : Received: 19 September 2020 / Approved: 20 September 2020 / Online: 20 September 2020 (15:20:52 CEST)

How to cite: Lee, C.S.; Song, I.H.; Lee, A.; Kang, J.; Lee, Y.S.; Lee, I.K.; Song, Y.S.; Lee, S.H. Enhancing the Landscape of Colorectal Cancer Using Targeted Deep Sequencing. Preprints 2020, 2020090483 (doi: 10.20944/preprints202009.0483.v1). Lee, C.S.; Song, I.H.; Lee, A.; Kang, J.; Lee, Y.S.; Lee, I.K.; Song, Y.S.; Lee, S.H. Enhancing the Landscape of Colorectal Cancer Using Targeted Deep Sequencing. Preprints 2020, 2020090483 (doi: 10.20944/preprints202009.0483.v1).

Abstract

Targeted next-generation sequencing (NGS) technology detects specific mutations that can provide treatment opportunities for colorectal cancer (CRC) patients. We included 145 CRC patients who underwent surgery. We analyzed the mutation frequencies of common actionable genes and their association with clinicopathological characteristics and oncologic outcomes using targeted NGS. Approximately 97.9% (142) of patients showed somatic mutations. Frequent mutations were observed in TP53 (70%), KRAS (49%), and APC (47%). TP53 mutations were significantly linked to higher overall stage (p=0.038) and lower disease-free survival (DFS) (p=0.039). ATM mutation was significantly associated with higher tumor stage (p=0.012) and shorter overall survival (OS) (p=0.041). Stage 3 and 4 patients with ATM mutations (p=0.023) had shorter OS, and FBXW7 mutation was significantly associated with shorter DFS (p=0.002). In multivariate Cox regression analysis, ATM mutation was an independent biomarker for poor prognosis of OS (p=0.022). TP53 and FBXW7 mutations are independent biomarkers for poor prognosis of DFS (p=0.042 and 0.030, respectively). A comprehensive analysis of the molecular markers for CRC can provide insights into the mechanisms underlying disease progression and help optimize a personalized therapy.

Subject Areas

next-generation sequencing; colorectal cancer; ATM mutation; FBXW7 mutation

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