ABSTRACT
AIMS: Adrenocortical carcinoma (ACC) carries a poor prognosis and current systemic cytotoxic therapies result in only modest improvement in overall survival. In this retrospective study, we performed a comprehensive genomic profiling of 29 consecutive ACC samples to identify potential targets of therapy not currently searched for in routine clinical practice. METHODS: DNA from 29 ACC was sequenced to high, uniform coverage (Illumina HiSeq) and analysed for genomic alterations (GAs). RESULTS: At least one GA was found in 22 (76%) ACC (mean 2.6 alterations per ACC). The most frequent GAs were in TP53 (34%), NF1 (14%), CDKN2A (14%), MEN1 (14%), CTNNB1 (10%) and ATM (10%). APC, CCND2, CDK4, DAXX, DNMT3A, KDM5C, LRP1B, MSH2 and RB1 were each altered in two cases (7%) and EGFR, ERBB4, KRAS, MDM2, NRAS, PDGFRB, PIK3CA, PTEN and PTCH1 were each altered in a single case (3%). In 17 (59%) of ACC, at least one GA was associated with an available therapeutic or a mechanism-based clinical trial. CONCLUSIONS: Next-generation sequencing can discover targets of therapy for relapsed and metastatic ACC and shows promise to improve outcomes for this aggressive form of cancer.
Subject(s)
Adrenal Cortex Neoplasms/drug therapy , Adrenal Cortex Neoplasms/genetics , Adrenocortical Carcinoma/drug therapy , Adrenocortical Carcinoma/genetics , Antineoplastic Agents/therapeutic use , Biomarkers, Tumor/genetics , Gene Expression Profiling/methods , High-Throughput Nucleotide Sequencing , Molecular Targeted Therapy , Adrenal Cortex Neoplasms/metabolism , Adrenal Cortex Neoplasms/pathology , Adrenocortical Carcinoma/metabolism , Adult , Aged , Biomarkers, Tumor/metabolism , Biopsy , Drug Design , Female , Genetic Predisposition to Disease , Humans , Male , Middle Aged , Patient Selection , Precision Medicine , Predictive Value of Tests , Retrospective Studies , Signal Transduction/drug effects , Signal Transduction/genetics , Young AdultABSTRACT
The "Marrainage" project involves the implementation and evaluation of an intervention to prevent negligence in at-risk families with at least one child between the age of 0 and 5. The goal of the intervention is to introduce into those families, working nonprofessionals who can help them create their own natural support network and improve the quality of the family environment. The sponsors offer the following support services: emotional support, counselling-information, physical assistance, social skills development, positive feedback, and material needs. The sponsors work most often with the mother. The services provided to children consist mainly of outings, games and personal care. Such interventions have positive effects on the family environment, particularly on the parents' abilities and the psychological well-being of the mother. On the other hand, there is no conclusive evidence of a positive impact on the use of the families' natural networks.
