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The analysis of circulating cell-free tumor DNA has remarkable potential for the detection and monitoring of cancers. Genetic alterations are present in virtually all types of cancers, allowing broad applicability of this approach regardless of the primary organ and histologic type of the cancer. To date only a few specific proteins and glycoproteins have been discovered that can be reliably used as tumor markers. Consequently, extensive efforts have been made over the last decade to identify cancer-associated genetic changes that might be suitable for use as new tumor markers. However, only a few of these genetic markers have been translated into clinical use. One major reason is that the genetic changes in cancer are very heterogeneous even within a single type of cancer. Therefore, it is difficult to achieve a high clinical sensitivity for cancer detection by targeting only one or even a few genetic markers. In a recent study by Dawson et al., an approach has been proposed for developing individualized tumor markers (1). As the first step of this approach, the tumor tissue of each cancer patient was sequenced by either targeted amplicon sequencing or whole-genome sequencing to identify cancer-specific single nucleotide changes and structural variants. The alterations identified were detected and quantified in the plasma of the corresponding patient with the use of digital PCR or targeted deep sequencing. Tumor samples from a total of 52 patients with metastatic breast cancer were analyzed using targeted sequencing to identify point mutations in the phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha ( PIK3CA )4 and tumor protein p53 ( TP53 ) genes (1). Twenty-five (48%) of the patients had at least one mutation detected using this method. Whole-genome sequencing was performed on tumor tissue samples from 9 of these individuals. Additional structural variants and/or single-nucleotide mutations were identified in all of the tumors …

Scanning for Cancer Genomic Changes in Plasma: Toward an Era of Personalized Blood-Based Tumor Markers