Dear Editor,Signet-ring cell carcinoma (SRCC) is a rare subtype of colorectal cancer (CRC) characterized histologically by the accumulation of mucins in the cytoplasm and displacement of nuclei to the cellular periphery,accounting for about 1％ CRC (Fig.S1A) (Borger et al.,2007).Compare to common subtypes of CRC,such as adenocarcinoma (AC) and mucinous adenocarcinoma (MAC),SRCC is associated with aggressive behaviors and younger age at presentation (Kang et al.,2005;Sung et al.,2008;Nitsche et al.,2013;Hugen et al.,2014;Inamura et al.,2015).A retrospective analysis of CRC patients data at Fudan University Shanghai Cancer Center (FUSCC) also indicated a worse overall and disease-free survival of SRCC patients (Fig.S1B and S1C,Table S1).Due to low incidence and occasionally mixed presence of SRCC with AC or MAC,genome-wide characterization of SRCC at a large scale is challenging.Limited whole-exome sequencing (n =5) and gene panel sequencing (n =35) results indicate that,most driver mutations associated with CRC,such as APC,KRAS,and PIK3CA,are mutated at lower rates in SRCC (Nam et al.,2018;Korphaisam et al.,2019).Mutations and signaling pathways responsible for the tumorigenesis of SRCC remains to be uncovered.