AUTHOR=Huang Liang , Luo Shuanglin , Zhang Xingwei , Cai Yonghua , Xue Fangqin , Hu Huanxin , Zeng Ziwei , Lin Tengjiao , Wang Fei , Wang Weifeng , Zhang Sen , Kang Liang 

TITLE=Distinct Genomic Landscape of Colorectal Mucinous Carcinoma Determined via Comprehensive Genomic Profiling: Steps to a New Treatment Strategy

JOURNAL=Frontiers in Oncology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.603564

DOI=10.3389/fonc.2021.603564

ISSN=2234-943X

ABSTRACT=<p>Colorectal mucinous carcinoma (MC) is associated with inferior prognosis and response to treatment compared to adenocarcinoma (AC). The molecular landscapes of MC and adenocarcinoma with mucous composition (AMC) are not well-defined. We aimed to describe the genomic landscape of MC and AMC in a large colorectal cancer cohort. Tumor samples from patients with MC, AMC, or AC were analyzed using next-generation sequencing. MC had a molecular signature distinct from that of AC; genomic features were similar between AMC and MC but not between AMC and AC. <italic>HER2</italic> amplification and <italic>TP53</italic> and <italic>APC</italic> mutation rates were lower, whereas <italic>SMAD4</italic>, <italic>PIK3CA</italic>, <italic>ACVR2A</italic>, <italic>KMT2D</italic>, <italic>LRP1</italic>, <italic>TGFBR2</italic>, <italic>GRIN2A</italic>, <italic>BRAF</italic> V600E, <italic>PTEN</italic>, and <italic>BRCA2</italic> mutation rates were higher in MC than in AC. The mutation frequencies in MAPK, PI3K, and TGF-β pathways were higher, whereas those of cell cycle proteins and Wnt were lower in MC and AMC than in AC. The proportion of hypermutated tumors was significantly higher in MC and AMC than in AC. As MC has a distinct molecular signature from AC, immunotherapy can be potentially applied in treating MC. Similar molecular profiles of AMC and MC suggest that treatment strategies for MC, but not AC, can be used for AMC treatment.</p>