“…Furthermore, the difficulty in discerning low-abundance unknown mutations is especially pronounced in heterogeneous specimens from precancerous or cancerous tissue biopsies, sputum, urine, stool and circulating extracellular DNA released in the blood. Similarly, as cancer cells are typically heterogeneous in infiltrating and multifocal cancer types, they will be present at low abundances among an excess of normal cells [10–12]. Tumors with high stromal contamination, such as those found in pancreatic, lung or prostate cancer, often contain mutations that are obscured by the relatively large abundance of wild-type alleles [4,10,13–15], and thus require laborious microdissection to isolate the tumor cells prior to performing molecular analyses.…”