Targeted profiling of 517 cancer genes in 39 colorectal signet-ring cell carcinomas found KMT2C and SMAD4 alterations in 49% each, while canonical drivers such as APC and KRAS appeared less often than typically reported in conventional adenocarcinoma. This points to epigenetic and TGF-β hypotheses but does not yet guide treatment.
Key findings
- TMB-high status occurred in 15.4%. KMT2C and SMAD4 alterations each occurred in 49%, followed by TP53 41%, CIC 31%, ZFHX3 28%, and KMT2A/KMT2D/CSMD3/ZMYM3 26% each. APC, KRAS, NRAS, BRAF and PIK3CA were 23%, 15%, 2.5%, 10% and 10%.
Why this matters globally
Colorectal SRCC is rare, aggressive and genomically undercharacterized. Thai data diversify precision-oncology evidence and generate targets for international cohorts.
Thai researcher contribution
Siriraj, Mahidol and Ramathibodi teams generated Thai genomic evidence for a subtype poorly represented globally.
Limitations to consider
Only 39 cases were studied without a same-platform conventional-CRC comparator. Targeted panels miss broader structural and epigenomic events, FFPE can introduce artifacts, and functional, survival and treatment-response validation are absent.