Cancer germline predisposing variants and late mortality from subsequent malignant neoplasms among long-term childhood cancer survivors: a report from the St Jude Lifetime Cohort and the Childhood Cancer Survivor Study.

Background: Carriers of cancer predisposing variants are at an increased risk of developing subsequent malignant neoplasms among those who have survived childhood cancer. We aimed to investigate whether cancer predisposing variants contribute to the risk of subsequent malignant neoplasm-related late mortality (5 years or more after diagnosis).

Methods: In this analysis, data were included from two retrospective cohort studies, St Jude Lifetime Cohort (SJLIFE) and the Childhood Cancer Survivor Study (CCSS), with prospective follow-up of patients who were alive for at least 5 years after diagnosis with childhood cancer (ie, long-term childhood cancer survivors) with corresponding germline whole genome or whole exome sequencing data.

Pathogenic Germline Mutations in DNA Repair Genes in Combination With Cancer Treatment Exposures and Risk of Subsequent Neoplasms Among Long-Term Survivors of Childhood Cancer.

Purpose: To investigate cancer treatment plus pathogenic germline mutations (PGMs) in DNA repair genes (DRGs) for identification of childhood cancer survivors at increased risk of subsequent neoplasms (SNs).

Methods: Whole-genome sequencing was performed on blood-derived DNA from survivors in the St Jude Lifetime Cohort. PGMs were evaluated in 127 genes from 6 major DNA repair pathways.

Structural Comparisons of PEI/DNA and PEI/siRNA Complexes Revealed with Molecular Dynamics Simulations.

Polyplexes composed of polyethyleneimine (PEI) and DNA or siRNA have attracted great attention for their use in gene therapy. Although many physicochemical characteristics of these polyplexes remain unknown, PEI/DNA complexes have been repeatedly shown to be more stable than their PEI/siRNA counterparts. Here, we examine potential causes for this difference using atomistic molecular dynamics simulations of complexation between linear PEI and DNA or siRNA duplexes containing the same number of bases.