1217P - Clinical evaluation of a CE-IVD liquid biopsy pan cancer genomic profiling test

Background

With the accessibility of precision therapies, a robust circulating cell-free total nucleic acid (cfTNA)-based pan-cancer NGS (Next Generation Sequencing) genomic profiling liquid biopsy (LB) test is a valuable addition to identify genomic signatures for the relevant treatment options, where tissue is not available. Liquid biopsy NGS tests also offer the advantage of continual detection of evolving tumor mutations in a minimally invasive way to help inform cancer patient management.

Methods

Here we report an analysis of SNV (Single Nucleotide Variant) hotspots, gene fusion, copy number amplification (CNA) from 52 recurrently mutated oncogenes, and tumor suppressor genes in 3630 cancer patients, belonging to 44 solid organ cancers. The study used a CE-IVD approved in vitro diagnostic Laboratory Developed test (LDT) from Datar Cancer Genetics. The technology employs NGS tag-sequencing approach to detect pan cancer biomarkers that may guide treatment decisions and management of patients. cfTNA was extracted from peripheral whole blood to prepare tag sequencing NGS libraries and the NGS data were processed using a custom analysis pipeline that can detect up to 0.1% mutant allele frequency.

Results

The SNV analysis revealed TP53 (38%) KRAS (11%), PIK3CA (10%) as the most recurrently mutated genes across cancer types. Distinct SNV clusters were observed across major cancer types such as ESR1, PIK3CA, TP53 in breast cancers, EGFR, GNAS, TP53 in lung cancer, APC, KRAS, TP53, PIK3CA in colorectal cancer. The highest CNA prevalence was observed in MYC, FGFR1, ERBB2, CCND1, CDK4 with cancer-specific signatures. TMPRSS2-ERG emerged as the most prevalent gene fusion, followed by MET and EML4-ALK. Cancers harboring most SNV mutations are colorectal, lung, pancreas, and uterine with an average >1 SNVs detected in all patients. Breast cancer patients harbored the highest number of CNAs followed by colorectal, lung and prostate cancer.

Conclusions

This comprehensive pan cancer cfTNA LB test evaluated on Asian and Caucasian cancer patients successfully identified relevant signatures of major genomic alternations of therapeutic, diagnostic, and prognostic significance that can provide confidence to physicians in the use of the test for their patients.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Datar Cancer Genetics, Nasik, India and Datar Cancer Genetics, Guildford, UK.

Funding

Datar Cancer Genetics, Nasik, India and Datar Cancer Genetics, Guildford, UK.

Disclosure

A. Gaya: Financial Interests, Personal, Stocks/Shares: Datar Cancer Genetics Pvt Ltd. All other authors have declared no conflicts of interest.