In coordination with Gynecologic Oncology Group 84th Semi-Annual Meeting in San Diego this week, AltheaDx has announced the launch of a next-generation sequencing (NGS) service designed to support clinical trials in the detection of mutations in genes encoding components of DNA repair and homologous recombination pathways. Modulation of these pathways is a current therapeutic strategy for some gynecologic cancers.
In particular, poly [ADP-ribose] polymerase 1 (PARP1 ) plays a central role in repair of single-stranded DNA (ssDNA) breaks. Inhibiting PARP1 activity with small molecules reduces repair of ssDNA breaks. In the absence of PARP1, when these breaks are encountered during DNA replication, the replication fork stalls, and double-strand DNA (dsDNA) breaks accumulate. These dsDNA breaks are repaired via homologous recombination (HR) repair. It is hypothesized that PARP1 inhibitors may prove highly effective as therapies for cancers with BRCA1/2 mutations, such as ovarian cancer, due to the high sensitivity of the tumors to the inhibitor and the lack of deleterious effects on the remaining healthy cells with functioning BRCA homologous recombination pathway. This is in contrast to conventional chemotherapies, which are highly toxic to all cells and can induce DNA damage in healthy cells, leading to secondary cancer generation.
AltheaDx provides NGS services using both the Life Technologies Ion Torrent PGM™ system and the Roche 454 GS Jr™ system with a total workflow solution starting from nucleic acid isolation, target enrichment, library construction and sequencing. The workflow exploits a NGS protocol that enriches for RefSeq defined UTR and exonic regions of genes encoding DNA repair and homologous recombination enzymes using targeted selection from genomic DNA. The digital nature and large dynamic range of targeted resequencing of clinical trial samples by NGS enables comparisons of genomic variations from both germline controls and tumor samples in order to identify tumor specific genetic variations (such as BRCA1/2 and RAD51 mutations) potentially aiding in the selection of clinical trial cohorts likely to respond to targeted therapeutics (such as PARP inhibitors).