Radiation Biology

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SU_39_2391 - Delineate Genomic and Epigenomic Changes in Esophageal Squamous Cell Carcinoma Following Radiation Therapy

Sunday, October 21
1:15 PM - 2:45 PM
Location: Innovation Hub, Exhibit Hall 3

Delineate Genomic and Epigenomic Changes in Esophageal Squamous Cell Carcinoma Following Radiation Therapy
S. Cui1, T. Song1, H. Zhang2, H. Wu1, L. Yang1, X. Zhang1, J. Yue1, Z. Jiang1, and S. Wu1; 1Hangzhou Cancer Institute, Hangzhou Cancer Hospital, Hangzhou, China, 2Hangzhou Cancer Hospital, Hangzhou, China

Purpose/Objective(s): Esophageal squamous cell carcinoma (ESCC) is one of the most common lethal cancers worldwide. Radiotherapy is the standard clinical treatment of ESCC. Understanding how radiotherapy affects esophageal squamous cancer cells is a key biological question. We investigated the molecular changes during radiotherapy on the bases of genetic and epigenetic features.

Materials/Methods: We performed whole-exome sequencing and genome-wide DNA methylation profiling of samples collected from different time points during radiotherapy from ESCC patients. We detected the genetic and epigenetic alterations of different samples at sequential time points to compare the pre-treated and treated samples following radiotherapy and explore the mutagenic mechanism shaping the evolution of ESCC.

Results: Our study provided several important insights: (i) The genomic changes during radiotherapy follow a gain and loss pattern and the treated samples may acquire mutations in known driver genes. (ii) DNA mismatch repair deficiency induced mutagenesis is enriched in treated ESCC and continues to shape the ESCC evolution following the radiotherapy. (iii) Methylome is also largely edited by ionizing radiation with a global trend towards hypomethylation after radiotherapy. (iv) By analyzing whole-exome sequencing data of 84 primary ESCC tumors, we identified an ESCC related driver gene (MUC16) which has not previously described in ESCC.

Conclusion: Our integrated study provides an important molecular foundation for understanding of tumor progression in ESCC during radiotherapy.

Author Disclosure: S. Cui: None. T. Song: None. H. Zhang: None. H. Wu: None.

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