Endocrine Abstracts

Laron syndrome (LS) is a rare genetic endocrinopathy that results from mutation or deletion of the growth hormone receptor (GH-R) gene. LS is the best characterized entity under the spectrum of the congenital insulin-like growth factor-1 (IGF1) deficiencies and is typically associated with dwarfism and obesity. Epidemiological studies have shown that LS patients do not develop cancer whereas heterozygous family members have a tumor prevalence similar to the general population. To identify genes and signaling pathways that are differentially expressed in LS and that may help delineate a biochemical and molecular basis for cancer protection, we conducted a genome-wide profiling of LS patients. Analyses were based on our collection of Epstein-Bar virus (EBV)-immortalized lymphoblastoid cell lines derived from LS patients, relatives and healthy controls. Bioinformatic analyses identified differences in gene representation in a number of pathways, including apoptosis, metabolic control, cytokine biology, Jak-STAT and PI3K-AKT signaling, etc. Genes involved in positive control of cell cycle, motility, growth and oncogenic transformation are, in general, down-regulated in LS patients. These genetic events seem to have a major impact on the biological properties of LS cells, including proliferation, apoptosis, response to oxidative stress, etc. Furthermore, genomic analyses allowed us to identify novel IGF1 downstream target genes that have not been previously linked to the IGF1 signaling pathway. In summary, by ‘mining’ genomic data from LS patients we were able to generate clinically-relevant information in oncology and, potentially, in other areas in which the IGF1 system is involved.