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- W4286296380 abstract "e15555 Background: Synchronous colorectal cancer (SCRC) refers to a special group of CRC with at least two primary tumors detected simultaneously in one patient, with 90% being sporadic. Although the systemic treatments of late-stage SCRC are mainly based on the molecular testing of one primary lesion, this might not be representable of the other tumors and metastatic lesions. This study aimed to investigate the molecular features and genetic heterogeneity of sporadic SCRC in order to guide clinical practice. Methods: We retrospectively collected all the primary tumor samples of 51 patients with sporadic SCRC, profiled 103 samples with whole-exome sequencing, and analyzed their molecular landscape and genomic profiles. We conducted comparative analyses between tumor pairs in one patient, and as well as between SCRC and solitary CRC. The evolutionary dynamics of SCRC tumors was also analyzed. Results: Most gene mutations and copy number variations were inconsistent in paired tumors except for early driving genes APC, TP53 and KRAS. No pathogenic germline variants of familial CRC-related genes were observed . Clonal composition analysis showed that tumors in 94.2% (48/51) of patients with SCRC were genetically heterogeneous. Only 7.8% (4/51) of patients harbored origin-shared tumors. Inconsistent MSI and TMB status were observed in 11.8% (6/51) of patients. For actionable RAS/ BRAF gene loci, 43.1% (22/51) of patients harbored tumor pairs sharing the same wild or mutant status. When compared with solitary CRC, SCRC had higher prevalence of MSI-H (29.4% vs. 12.0-17.0%) or TMB-H (33.3% vs. 10.0-16.0%) and lower mutational frequencies in the RTK/RAS (51.5% vs. 76.1%), PI3K (26.2% vs. 43.4%) and cell-cycle (2.9% vs. 10.2%) oncogenic signaling pathways. Moreover, neutral evolution analysis showed that 84.3% (43/51) of patients had at least one neutral tumor and 45.1% (23/51) of patients had tumors evolving differently. Conclusions: Sporadic SCRC was a special subclass of CRC, featured by prominent TMB-H, dMMR-related signatures, and intertumoral genetic heterogeneity. The tumors from the same SCRC patient tended to have different origins and evolved differently. Thus, clinical treatment strategies for sporadic SCRC should be re-evaluated accordingly." @default.
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- W4286296380 date "2022-06-01" @default.
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- W4286296380 title "Mutational profiles of sporadic synchronous colorectal cancer." @default.
- W4286296380 doi "https://doi.org/10.1200/jco.2022.40.16_suppl.e15555" @default.
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