No evidence for genetic differentiation in juvenile traits between Belgian and French populations of the invasive tree Robinia pseudoacacia

Background – The role of evolution in biological invasion studies is often overlooked. In order to evaluate the evolutionary mechanisms behind invasiveness, both quantitative and population genetics studies are underway on Robinia pseudoacacia L., one of the worst invasive tree species in Europe.Methods – A controlled experiment was set up using 2000 seeds from ten populations in Southern France and ten populations in Belgium. Seedlings were cultivated in two climatic chambers set at 18°C and 22°C. Early development life history traits (e.g. seedling phenology) and functional traits (e.g. growth rates) were monitored. Genotyping using SNP markers was used to evaluate the genetic differentiation among the populations and a QST – FST comparison was done in order to test for the role of selection.Results – Populations exhibited a strong plasticity to temperature for all measured traits, the warmer environment being generally more suitable, irrespective of their origin. No significant departure from neutral evolution was evidenced by the QST – FST comparisons, although we found a slightly significant differentiation at the molecular level. Conclusion – Plasticity for the functional and life history traits was evidenced but no genetic interaction suggesting no possible evolution of plasticity at those traits. Moreover, no support for genetic differentiation and local adaptation was found among studied populations within invasive range, raising two main questions: first, what is the role of selection on functional and life-history traits; and second, is the elapsed time since first introduction sufficient to allow evolution and local adaptation

Clinical impact of extensive molecular profiling in advanced cancer patients

Abstract Previous precision medicine studies have investigated conventional molecular techniques and/or limited sets of gene alterations. The aim of this study was to describe the impact of the next-generation sequencing of the largest panel of genes used to date in tumour tissue and blood in the context of institutional molecular screening programmes. DNA analysis was performed by next-generation sequencing using a panel of 426 cancer-related genes and by comparative genomic hybridization from formalin-fixed and paraffin-embedded archived tumour samples when available or from fresh tumour samples. Five hundred sixty-eight patients were enrolled. The median number of prior lines of treatment was 2 (range 0–9). The most common primary tumour types were lung (16.9%), colorectal (14.4%), breast (10.6%), ovarian (10.2%) and sarcoma (10.2%). The median patient age was 63 years (range 19–88). A total of 292 patients (51.4%) presented with at least one actionable genetic alteration. The 20 genes most frequently altered were TP53, CDKN2A, KRAS, PTEN, PI3KCA, RB1, APC, ERBB2, MYC, EGFR, CDKN2B, ARID1A, SMAD4, FGFR1, MDM2, BRAF, ATM, CCNE1, FGFR3 and FRS2. One hundred fifty-nine patients (28%) were included in early phase trials. The treatment was matched with a tumour profile in 86 cases (15%). The two main reasons for non-inclusion were non-progressive disease (31.5%) and general status deterioration (25%). Twenty-eight percent of patients presented with a growth modulation index (time to progression under the early phase trial treatment/time to progression of the previous line of treatment) >1.3. Extensive molecular profiling using high-throughput techniques allows for the identification of actionable mutations in the majority of cases and is associated with substantial clinical benefit in up to one in four patients

Molecular profiling of advanced soft-tissue sarcomas: the MULTISARC randomized trial

Background: Soft-tissue sarcomas (STS) represent a heterogeneous group of rare tumors including more than 70 different histological subtypes. High throughput molecular analysis (next generation sequencing exome [NGS]) is a unique opportunity to identify driver mutations that can change the usual one-size-fits-all treatment paradigm to a patient-driven therapeutic strategy. The primary objective of the MULTISARC trial is to assess whether NGS can be conducted for a large proportion of metastatic STS participants within a reasonable time, and, secondarily to determine whether a NGS-guided therapeutic strategy improves participant's outcome. Methods: This is a randomized, multicentre, phase II/III trial inspired by the design of umbrella and biomarker-driven trials. The setting plans up to 17 investigational centres across France and the recruitment of 960 participants. Participants aged at least 18 years, with unresectable locally advanced and/or metastatic STS confirmed by the French sarcoma pathological reference network, are randomized according to 1:1 allocation ratio between the experimental arm "NGS" and the standard "No NGS". NGS will be considered feasible if (i) NGS results are available and interpretable, and (ii) a report of exome sequencing including a clinical recommendation from a multidisciplinary tumor board is provided to investigators within 7 weeks from reception of the samples on the biopathological platform. A feasibility rate of more than 70% is expected (null hypothesis: 70% versus alternative hypothesis: 80%). In terms of care, participants randomized in "No NGS" arm and who fail treatment will be able to switch to the NGS arm at the request of the investigator. Discussion: The MULTISARC trial is a prospective study designed to provide high-level evidence to support the implementation of NGS in routine clinical practice for advanced STS participants, on a large scale. Trial registration: clinicaltrial.gov NCT03784014