Comprehensive Sequencing of Metastatic Prostate Cancer Identifies Clinically Significant Subgroups
Posted: Friday, July 27, 2018
By using whole-genome sequencing, international investigators were able to identify an increased frequency of alterations in certain driver genes in patients with metastatic prostate cancer, which may indicate their role in dissemination and/or treatment failure, according to a study featured at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract 5014). Martijn P. Lolkema, MD, PhD, of the Erasmus MC Cancer Institute in Rotterdam, Netherlands, and colleagues, used their findings to categorize patients into clinically relevant groups for targeting by future treatments.
A total of 153 patients with metastatic prostate cancer were included in this study. The sites of fresh-frozen tissue biopsy included the lymph node, bone, and viscera. Dr. Lolkema and colleagues reviewed sequencing data for instances of tumor-specific single-nucleotide variants, copy number alterations, small insertions and deletions, and chromosomal rearrangements. They then compared these occurrences with those reported for primary disease, leading to the recognition of clinically significant subgroups based on microsatellite instability, BRCAness, PI3K, and RB.
The researchers identified 69 and 62 alterations in the driver genes ARand TP53. Their study results showed that the median occurrence of single-nucleotide variants was 2.6 per million base pairs, almost 5 times higher than that in primary disease (0.53 per million base pairs). The median number of interchromosomal rearrangements (58) was also significantly higher than that in primary disease (19). Overall, the median tumor cell content of the biopsy samples was 60%.
