Discordance of mutational signatures between pretreatment tumor tissue and circulating tumor DNA in patients with metastatic SCCA

A retrospective study at Vanderbilt University Medical Center (Nashville, TN) compared genomic alterations between pretreatment tumor tissue and posttreatment circulating tumor DNA (ctDNA) in patients with metastatic squamous cell carcinoma of the anal canal (mSCCA). Among the mutations identified with next-generation sequencing in posttreatment ctDNA, 34.5% were also found in pretreatment tumor tissue, while 47.6% of pretreatment tumor tissue mutations were found in posttreatment ctDNA. Thirty-six percent of patients had preservation of potentially actionable mutations in both pretreatment tissue and posttreatment ctDNA, while 64% of patients had newly identified mutations in posttreatment ctDNA that were not present in pretreatment tumor tissue. The authors conclude that patients with mSCCA demonstrate a high degree of temporal mutational heterogeneity, and that these results highlight the potential of ctDNA analysis in identifying emerging actionable mutations in this relatively rare tumor type.