The mutational landscape of circulating cell free DNA in patients with colorectal adenoma and carcinoma

Author:Ying Hu, Hao Guo, Yawei Chen, Yanhui Chen, Ling Lan, Jian Li, Henghui Zhang

Background & Aims: This study was designed to explore the plasma cell free DNA (cfDNA) mutation profile in the pathological progression of colorectal cancer. In addition, we aimed to illustrate the difference mutation profile among the left-sided colon, right-sided colon, and rectal carcinoma.

Methods: Tumor tissue and matched blood samples were collected from Henan Provincial People’s Hospital between March 2016 and January 2017.This cohort included 9 cases of colon polyps, 18 cases of colon adenoma, 26 cases of colon cancer, 24 cases of rectal cancer. Tissue DNA, the plasma cfDNA and leukocytes DNA were isolated. The mutation profile of plasma cfDNA in the process of adenoma-to-carcinoma was sequenced using a modified cancer gene panel.

Results: The plasma cfDNA concentrations and somatic mutation burden of colon carcinoma were significantly higher than those in colon polyp and adenoma group. The tumor mutation burden (TMB) in tissue DNA is positively correlated with the TMB in plasma cfDNA. A biomarker combination including the CEA protein level, the plasma cfDNA concentration, and cfDNA mutation burden achieved an area of 0.80 under the receiver operation characteristic curve for diagnosis of CRC. The diagnosis power of the combination model was superior to that of CEA alone. 

Furthermore,the somatic DNA alteration landscapes are different among the left-sided, right-sided, and rectal cancer. Compared with the life-sided colon, the right-sided colon cancer tumor tissue harbors more gene mutations. And the TMB value of the right-sided colon cancer was significantly higher than those in the life-sided colon and rectal-sided colon cancer (P<0.05).

Conclusions: The somatic mutations of plasma cfDNA may be potential biomarkers for diagnosis colorectal cancer. Compared with left-sided colon, the somatic mutations of right-sided colon cancer involved more genes and pathways.