Identification of growth processes involved in QTLs for tomato fruit size and composition

Many quantitative trait loci (QTLs) for quality traits have been located on the tomato genetic map, but introgression of favourable wild alleles into large fruited species is hampered by co-localizations of QTLs with antagonist effects. The aim of this study was to assess the growth processes controlled by the main QTLs for fruit size and composition. Four nearly isogenic lines (NILs) derived from an intraspecific cross between a tasty cherry tomato (Cervil) and a normal-tasting large fruit tomato (Levovil) were studied. The lines carried one (L2, L4, and L9) or five (Lx) introgressions from Cervil on chromosomes 1, 2, 4, and 9. QTLs for fruit size could be mainly associated with cell division processes in L2 and L9, whereas cell expansion was rather homogeneous among the genotypes, except Cervil for which the low expansion rate was attributed to low cell plasticity. The link between endoreduplication and fruit size remained unclear, as cell or fruit sizes were positively correlated with the cell DNA content, but not with the endoreduplication factor. QTLs for fruit composition reflected differences in water accumulation rather than in sugar accumulation, except in L9 for which the up-regulation of sucrose unloading and hexose transport and/or starch synthesis was suggested. This may explain the increased amount of carbon allocated to cell structures in L9, which could be related to a QTL for fruit texture. In Lx, these effects were attenuated, except on fruit size and cell division. Finally, the region on top of chromosome 9 may control size and composition attributes in tomato, by a combination of QTL effects on cell division, cell wall synthesis, and carbon import and metabolism

Cutaneous adverse events in children treated with vemurafenib for refractory BRAF

International audienceAbstract Background The somatic BRAF V600E mutation occurs in 38–64% of pediatric cases of Langerhans cell histiocytosis (LCH). Vemurafenib (VMF), a BRAF inhibitor, was approved for refractory BRAF V600E mutated LCH. In adults, VMF causes frequent cutaneous adverse events (CAE) including skin tumors (squamous cell carcinomas, melanomas), but little is known in children. The objective of this study was to evaluate the frequency, clinical spectrum, and severity of CAEs in children treated with VMF for LCH. In addition, a correlation between CAE occurrence and VMF dose, residual plasma levels (RPLs), and efficacy was searched for. Procedure Multicentric retrospective observational study including patients <18 years treated with VMF alone for refractory BRAF V600E mutated LCH in 13 countries between October 1, 2013 and December 31, 2018. Results Fifty‐seven patients: 56% female, median age 2.1 years (0.2–14.6), median treatment duration 4.1 months (1.4–29.7). Forty‐one patients (72%) had at least one CAE: photosensitivity (40%), keratosis pilaris (32%), rash (26%), xerosis (21%), and neutrophilic panniculitis (16%). No skin tumor was observed. Five percent of CAEs were grade 3. None were grade 4 or led to permanent VMF discontinuation. Dose reduction was necessary for 12% of patients, temporary treatment discontinuation for 16%, none leading to loss of efficacy. VMF dose, median RPL, and efficacy were not correlated with CAE occurrence. Conclusions At doses used for pediatric LCH, CAEs are frequent but rarely severe and have little impact on the continuation of treatment when managed appropriately. Regular dermatological follow‐up is essential to manage CAEs and screen for possible induced skin tumors

CUTANEOUS ADVERSE EVENTS IN CHILDREN TREATED WITH BRAF-INHIBITOR VEMURAFENIB FOR REFRACTORY BRAF (V600E) MUTATED LANGERHANS CELL HISTIOCYTOSIS: A EUROPEAN COHORT STUDY

International audienc

Epstein–Barr Virus‐Associated Smooth Muscle Tumor After Kidney Transplantation: A French Multicenter Retrospective Study

International audienceBackground : Epstein–Barr virus (EBV) is a herpesvirus linked to nine different human tumors and lymphoproliferative disorders. Immunosuppression promotes EBV‐driven malignancies. The most frequent EBV‐induced malignancies are lymphomas and nasopharyngeal carcinoma. By promoting smooth muscle proliferation, EBV can induce EBV‐associated smooth muscle tumors (EBV‐SMT). EBV‐SMT is a rare oncological entity for which no current guideline for diagnosis or management exists. Data on posttransplant EBV‐SMT (PT‐SMT) are scarce in kidney transplant recipients. Methods : We conducted a national multicentric retrospective study and collected cases among transplantation centers in France. Kidney transplant recipients experiencing histologically proven PT‐SMT were included. We collected data on demographic characteristics of patient, history of kidney transplantation, history of PT‐SMT, evolution of graft function, and patient survival. Results : Eight patients were included. The median age at PT‐SMT diagnosis was 31 years (range 6.5–40). PT‐SMT occurred after a median delay of 37.8 months after transplantation (range 6–175). PT‐SMT management consisted in immunosuppressive regimen minimization in all patients. Introduction of mTOR inhibitors was performed in two patients. Four patients (50%) needed chemotherapy. Surgical resection was performed in four patients. At last follow‐up after PT‐SMT diagnosis (median 33 months (range 17–132)), five patients were considered in complete remission, and two patients had died. Two patients experienced graft rejection; two resumed dialysis (25%). All patients with available data presented with impaired graft function at last follow‐up. Conclusion : PT‐SMT is a subacute and progressive disease during kidney transplantation. Even if the risk of developing PT‐SMT is low in kidney transplant recipients (0.07% in our cohort), PT‐SMT is associated with significant graft loss, possibly due to reduced immunosuppression. Developing guidelines could help transplantation teams better manage these patients

VEMURAFENIB IN CHILDREN WITH REFRACTORY LCH: 53 PATIENTS TREATED IN EU AND LEBANON

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Bibliographie critique

Eisemann Pierre Michel, Boeglin-Naumovic Nicolas, Buzzi Alessandro, Bannelier-Christakis Karine, Cosnard Michel, Daudet Yves, Decaux Emmanuel, Ecalle Adeline, Gérard Caroline, Legendre Mathilde, Maljean-Dubois Sandrine, Manouvel Mita, Morosoli Anthony, Moulier Isabelle, Peyro Llopis Ana, Robert Sabrina, Tardieu Aurélie, Tigroudja Hélène. Bibliographie critique. In: Annuaire français de droit international, volume 48, 2002. pp. 854-907