Germline mutations in pediatric cancer cohort with mixed-ancestry Mexicans.

BACKGROUND: Childhood cancer is one of the primary causes of disease-related death in 5- to 14-year-old children and currently no prevention strategies exist to reduce the incidence of this disease. Childhood cancer has a larger hereditary component compared with cancer in adults. Few genetic studies have been conducted on children with cancer. Additionally, Latin American populations are underrepresented in genomic studies compared with other populations. Therefore, the aim of this study is to analyze germline mutations in a group of mixed-ancestry Mexican pediatric patients with solid and hematological cancers. METHODS: We analyzed genetic variants from 40 Mexican childhood cancer patients and their relatives. DNA from saliva or blood samples was used for whole-exome sequencing. All variants were identified following GATK best practices. RESULTS: We found that six patients (15%) were carriers of germline mutations in CDKN2A, CHEK2, DICER1, FANCA, MSH6, MUTYH, NF1, and SBDS cancer predisposition genes, and additional new variants predicted to be deleterious by in silico algorithms. A population genetics analysis detected five components consistent with the demographic models assumed for modern mixed-ancestry Mexicans. CONCLUSIONS: This report identifies potential genetic risk factors and provides a better understanding of the underlying mechanisms of childhood cancer in this population.

The genetic era of childhood cancer: Identification of high-risk patients and germline sequencing approaches.

Childhood cancer is a leading cause of death by disease in children ages 5-14, for which there are no preventive strategies. Due to early-age of diagnosis and short period of exposure to environmental factors, increasing evidence suggests childhood cancer could have strong association with germline alterations in predisposition cancer genes but, their frequency and distribution are largely unknown. Several efforts have been made to develop tools to identify children with increased risk of cancer who may benefit from genetic testing but their validation and application on a large scale is necessary. Research on genetic bases of childhood cancer is ongoing, in which several approaches for the identification of genetic variants related to cancer predisposition have been used. In this paper, we discuss the updated efforts, strategies, molecular mechanisms and clinical implications for germline predisposition gene alterations and the characterization of risk variants in childhood cancer.

Myricetin suppresses lipoteichoic acid-induced interleukin-1ß and cyclooxygenase-2 expression in human gingival fibroblasts.

Periodontitis is an inflammatory disease affecting the connective tissue and supporting bone surrounding the teeth. In periodontitis, human gingival fibroblasts (HGFs) synthesize IL-1ß, causing a progressive inflammatory response. Flavones demonstrate a variety of biological activity: among others, they possess anti-inflammatory properties. Myricetin is a flavone with a strong anti-inflammatory activity. The objective of this study was to evaluate the effect of the flavonoid myricetin on HGFs under inflammatory conditions induced by lipoteichoic acid (LTA). the effect of myricetin on HGFs was assessed by measuring cell viability, signaling pathways and IL-1ß expression and synthesis. It was found that, over time, myricetin did not affect cell viability. However, it inhibited activation of p38 and extracellular-signal-regulated kinase-1/2 in LTA-treated HGFs and also blocked IκB degradation and cyclooxygenase-2 and prostaglandin E2 synthesis and expression. These findings suggest that myricetin has therapeutic effects in the form of controlling LTA-induced inflammatory responses.