Genomic profiling for copy number changes in plasma of ovarian cancer patients – a new era for cancer diagnostics?

Abstract

A blood test that can detect human malignancy with high clinical sensitivity and specificity is highly desirable. To achieve this, a tumor marker is needed that correlates with tumor burden and that can be measured with high analytical sensitivity and specificity. Over the past decades, a number of different types of tumor markers have emerged, including proteins such as enzymes, glycoproteins, and oncofetal antigens. Besides proteins, genetic abnormalities such as mutations, amplifications, and circulating tumor DNA have served as tumor markers. Despite the diversity of such biomarkers, their acceptance and implementation into routine clinical practice requires that their use results in improvements in patient outcome. Current tumor markers used in the clinic have limited utility. As such, innovative approaches to identifying tumor markers are highly desirable and one such approach may be to look for sub-chromosomal changes in the blood of patients with ovarian cancer, as is routinely performed in prenatal screening.Please see related article: http://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-016-0667-6

Liquid biopsy in ovarian cancer: recent advances on circulating tumor cells and circulating tumor DNA

“…They detected 40.6% of all HGSC cases, and more specifically, 38% of early stages, indicating a potential utility for early HGSC screening in plasma cfDNA based on specific multiple segmental chromosome gains and losses [51]. However, more validation studies along with the improvement of pre-analytical conditions and the examination of paired tumor DNA are needed before the routine application of this approach [74].…”

Circulating Tumor Cell-Free DNA Genes as Prognostic Gene Signature for Platinum Resistant Ovarian Cancer Diagnosis

“… 78 cfDNA based biomarkers are investigated widely for methylation patterns and DNA copy number variations in ovarian cancer patients. 79 , 80 Advances in next generation sequencing allowed our approach to sequence the minimal quantity of cfDNA for gene signature panels. 81 Although, the level of amplification of the considered genes may be low, this pilot project indicates presence of specific genes as cfDNA fragments in serum and respective protein expression levels in tumor tissue, which of those can be exploited further as multi-factorial definition for prognosis determination in ovarian cancer patients.…”

Applying low coverage whole genome sequencing to detect malignant ovarian mass

“…In recent years, the rapid development in the field of next generation sequencing (NGS) and its application in low coverage whole genome sequencing (LCWGS) makes the detection of tumor-specific copy number alterations (CNA) in cell-free DNA feasible [ 10 , 11 ]. Evidence has showed that tumor-derived chromosome abnormalities would be detectable in the plasma of patients prior to surgery [ 10 , 12 ].…”