Abstract
Detecting low-abundance mutations is very important for cancer diagnosis and treatment. Here we describe an improved targeted sequencing analysis that dramatically increases sequencing depth. Seven colorectal cancer (CRC) patients and seven healthy adults were enrolled in this study. We examined genetic mutations in tissue samples from the central and peripheral regions of tumors from the CRC patients and in blood cells from the healthy adults. We observed that each CRC carried larger numbers of mutations more than previously estimated. These included numerous deletion mutations in the tumor tissue. While the cellular morphology in the surrounding normal colonic tissues was healthy, these cells also carried many mutations. Similarly, the blood cells from the healthy donors carried numerous mutations. These findings shed new light on the processes of tumorigenesis and aging, and also present a potentially effective method for detecting low-abundance mutations for cancer diagnosis and targeted treatments.
Highlights
Cancers result in part from the accumulation of genetic mutations, which are caused by multiple intrinsic factors, such as errors during cell proliferation and DNA repair, and extrinsic factors, such as UV light and aflatoxins [1,2,3]
We examined genetic mutations in tissue samples from the central and peripheral regions of tumors from the colorectal cancer (CRC) patients and in blood cells from the healthy adults
When we compared the mutated genes from the healthy donors and patients based on mutation frequency and gene function, we found that there was a large number of mutations in the healthy donors that were shared by CRC patients (Figure 4C)
Summary
Cancers result in part from the accumulation of genetic mutations, which are caused by multiple intrinsic factors, such as errors during cell proliferation and DNA repair, and extrinsic factors, such as UV light and aflatoxins [1,2,3]. Mutation of RB, the first successfully cloned tumor suppressor gene, triggers the occurrence of retinoblastoma [5]. The apparent and direct causal associations between genetic mutations and cancer are infrequent; the roles of most mutations in cancer remain obscure. There are useful online mutation databases, such as COSMIC, it is very difficult to account for all the mutations that occur in all genes in cancer [6]. There may be large numbers of mutations within each gene. Compared to wild-type genes, mutant genes may acquire new functions, most of which have not been clearly identified [8, 9]
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