Clinicopathological and molecular features of genome-stable colorectal cancers

Abstract Colorectal cancers (CRCs) are traditionally divided into CRCs with either chromosomal instability (CIN) or microsatellite instability (MSI). By utilizing TCGA data, the Laird team found a subset of CRCs, namely, genome stable CRCs (GS CRCs), which lack both CIN and MSI. Although the molecular features of GS CRCs have been described in detail, the clinicopathological features are not well defined. A total of 437 CRCs were analyzed for copy number variation (CNV) statuses in 8 genes (ARID1A, EGFR, FGFR1, KDM5B, MYBL2, MYC, SALL4, and SETDB1) using droplet-digital PCR. CRCs that showed CNV in ≤one gene and no MSI were defined as GS CRCs. Clinicopathological and molecular features of GS CRCs were compared with those of CIN CRCs. GS CRCs comprised 4.6% of the CRCs. Compared with the CIN subtype,the GS subtype showed a predilection toward the proximal colon, lower nuclear optical density, KRAS mutation, PIK3CAmutation, and aberrant expression of KRT7. Survival analysis showed no significant difference between the three subgroups. Through our study, the GS subtype was found to comprise a minor proportion of CRCs and have proclivity toward proximal bowel location, hypochromatic tumor nuclei, aberrant KRT7 expression, and a high frequency of KRAS and PIK3CA mutations.