Cellular Barcoding Identifies Clonal Substitution as a Hallmark of Local Recurrence in a Surgical Model of Head and Neck Squamous Cell Carcinoma

Local recurrence after surgery for head and neck squamous cell carcinoma (HNSCC) remains a common event associated with a dismal prognosis. Improving this outcome requires a better understanding of cancer cell populations that expand from postsurgical minimal residual disease (MRD). Therefore, we assessed clonal dynamics in a surgical model of barcoded HNSCC growing in the submental region of immunodeficient mice. Clonal substitution and massive reduction of clonal heterogeneity emerged as hallmarks of local recurrence, as the clones dominating in less heterogeneous recurrences were scarce in their matched primary tumors. These lineages were selected by their ability to persist after surgery and competitively expand from MRD. Clones enriched in recurrences exhibited both private and shared genetic features and likely originated from ancestors shared with clones dominating in primary tumors. They demonstrated high invasiveness and epithelial-to-mesenchymal transition, eventually providing an attractive target for obtaining better local control for these tumors

Groundwater recharge estimation using chloride, stable isotopes and tritium profiles in the sands of northwestern Senegal

A study of environmental chloride, deuterium, oxygen-18, and tritium in deep sand profiles (35 m) has been carried out in order to estimate their relative value for measuring average groundwater recharge. The investigation was located at a 0.1-km2 site in Quaternary sands near the northwestern coast of Senegal in a zone of rainfed agriculture. By using a steady-state model for duplicate unsaturated zone chloride profiles, the long-term average recharge at the site was estimated to be 30 mm yr–1 or around 10% of the average precipitation (290 mm). The chloride concentration of adjacent shallow groundwater was relatively uniform and comparable to the unsaturated zone average, while the spatial variability in the depth distribution of Cl– in the unsaturated zone was considerable. Stable isotope (deuterium and oxygen-18) data show that there is some isotopic enrichment due to direct evaporation through the soil surface. The degree of heavy isotope enrichment is proportional to the extent of evaporative loss and there is good correspondance with the chloride enrichment. Nevertheless, stable isotopes cannot be used quantitatively to estimate the recharge. The excellent preservation of the peak in thermonuclear tritium in precipitation in the unsaturated zone at depths between 12 and 20 m enables an estimated annual recharge of 24 mm yr–1 in this area to be calculated, using the piston flow model. Agreement therefore between Cl and3H as tools for recharge measurement is reasonable over the site