2019-10-27 by Quick Biology Inc.
The Cancer Genome Atlas (TCGA) Program has sequenced over 20, 000 cancers of 33 cancer types (https://www.cancer.gov/about-nci/organization/ccg/research/structural-genomics/tcga), and revealed many mutational signatures underlying the biological process. However, cancers are end stages of an evolutionary process, which commonly arise through the accumulation of several driver mutations that engender a series of cancer cell clonal expansions.
In recent Nature, scientists in Wellcome Sanger Institute did whole genome sequencing of normal colorectal epithelial cells of 42 individuals (ref1). they systematically analyzed the earliest phases of colorectal neoplastic changes. Signatures of multiple mutational processes were revealed (Fig 1). They found TMB (tumor mutational burden: https://www.bms.com/modals/tmb.html) was higher in middle-aged, old-aged individuals (Fig 2). They also found some mutations were only found in some individuals, or even during certain periods of life, indicating that adenomas and carcinomas are rare outcomes of a pervasive process of neoplastic change. The work provides quantitative insight into the genomic and clonal evolution of cancer.
Figure 1: Mutations occur in normal colon. Examples of single-base substitution (SBS), doublet-base substitution (DBS) and small insertion and deletion (indel) (ID) mutational signatures. (ref1)
Figure 2: Mutational burden versus age for every signature. For every signature, the median (horizontal bar) and range (vertical bar) in mutational burden for all the crypts from each individual are shown. Each individual is colored differently. n = 445 crypts from 42 individuals.
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Reference:
- 1. Lee-Six, H. et al. The landscape of somatic mutation in normal colorectal epithelial cells. Nature (2019) Vol574:532-.