Throughout an individual’s lifetime, genomic alterations accumulate in somatic cells^1–11. However, the mutational landscape induced by retrotransposition of long interspersed nuclear element-1 (L1), a widespread mobile element in the human genome^12–14, is poorly understood in normal cells. Here we explored the whole-genome sequences of 899 single-cell clones established from three different cell types collected from 28 individuals. We identified 1,708 somatic L1 retrotransposition events that were enriched in colorectal epithelium and showed a positive relationship with age. Fingerprinting of source elements showed 34 retrotransposition-competent L1s. Multidimensional analysis demonstrated that (1) somatic L1 retrotranspositions occur from early embryogenesis at a substantial rate, (2) epigenetic on/off of a source element is preferentially determined in the early organogenesis stage, (3) retrotransposition-competent L1s with a lower population allele frequency have higher retrotransposition activity and (4) only a small fraction of L1 transcripts in the cytoplasm are finally retrotransposed in somatic cells. Analysis of matched cancers further suggested that somatic L1 retrotransposition rate is substantially increased during colorectal tumourigenesis. In summary, this study illustrates L1 retrotransposition-induced somatic mosaicism in normal cells and provides insights into the genomic and epigenomic regulation of transposable elements over the human lifetime.

Kwon HW, et al. J Korean Med Sci. 2016 Feb;31(Suppl 1):S69-S74. https://doi.org/10.3346/jkms.2016.31.S1.S69

Somatic cells accumulate genomic alterations with age; however, our understanding of mitochondrial DNA (mtDNA) mosaicism remains limited. Here we investigated the genomes of 2,096 clones derived from three cell types across 31 donors, identifying 6,451 mtDNA variants with heteroplasmy levels of ≳0.3%. While the majority of these variants were unique to individual clones, suggesting stochastic acquisition with age, 409 variants (6%) were shared across multiple embryonic lineages, indicating their origin from heteroplasmy in fertilized eggs. The mutational spectrum exhibited replication-strand bias, implicating mtDNA replication as a major mutational process. We evaluated the mtDNA mutation rate (5.0 × 10⁻⁸ per base pair) and a turnover frequency of 10–20 per year, which are fundamental components shaping the landscape of mtDNA mosaicism over a lifetime. The expansion of mtDNA-truncating mutations toward homoplasmy was substantially suppressed. Our findings provide comprehensive insights into the origins, dynamics and functional consequences of mtDNA mosaicism in human somatic cells.

Cyst infection (CI) is a common problem in patients with autosomal dominant polycystic kidney disease (ADPKD) and the accurate detection of infected cysts is very important. We evaluated the diagnostic performance of fluorine-18 fluorodeoxyglucose-labeled white blood cell (WBC) PET/computed tomography (CT) for detection of infected cysts in patients with ADPKD. Seventeen patients with ADPKD (male : female, 6 : 11; age, 53±9 years) and suspected CI were enrolled in this prospective study. Patients were classified as having definite/probable/possible CI. All patients underwent WBC PET/CT within 2 days of starting antibiotic treatment. The degree of WBC accumulation was evaluated qualitatively by nuclear medicine physicians. The diagnostic performance of WBC PET/CT was evaluated by sensitivity, specificity, positive predictive values, and negative predictive values. These values were compared with those generated from CT scans and MRI. Seven patients were classified as having renal CI (definite 6, probable 1). In this group, WBC PET/CT showed six positive findings and one equivocal finding. Seven patients were diagnosed with possible infection. In this group, WBC PET/CT showed six negative findings and one indeterminate finding. The diagnostic performance of WBC PET/CT showed advantages over CT or MRI scans (sensitivity 85.7%, specificity 87.5%, positive predictive value 85.7%, negative predictive value 87.5%). This prospective study shows that WBC PET/CT can provide an accurate diagnosis of CI in patients with ADPKD.