Getting the most out of limited samples

Comprehensive genomic profiling (CGP) is central to precision oncology, enabling biomarker discovery and trial optimization through next-generation sequencing (NGS). However, limited or degraded tumor tissue, especially from formalin-fixed paraffin-embedded (FFPE) samples, often compromises nucleic acid quality and sequencing outcomes.

We spoke with Dr. Erin Newburn, PhD, director of field applications at Labcorp, about how biopharma is addressing sample limitations through optimized workflows and scalable solutions, enabling high-quality genomic data from low-input, challenging material.

Q: Dr. Newburn, why is CGP a valuable tool in oncology today?

A: CGP allows us to move beyond a one-size-fits-all approach to cancer treatment. By using NGS, we identify actionable mutations for targeted treatments and immunotherapies. However, the success of CGP hinges on obtaining high-quality nucleic acid from samples, which is often easier said than done. Many samples are degraded or extremely limited in quantity, especially when working with core needle biopsies.

“Many labs struggle with limited or poor-quality samples, impacting sequencing success rates. By integrating automated, standardized processing workflows, we can significantly improve nucleic acid yield and quality, leading to more successful genomic profiling,” notes Dr. Newburn.

Q: How widespread are these sample quality issues in clinical research?

A: They’re highly prevalent. Clinical trial samples often come from FFPE blocks with nucleic acid yields in the low-nanogram range. These samples frequently exhibit degradation or cross-linking that challenges extraction and library preparation.

Q: What technical strategies have proven effective in addressing these challenges?

A: An impactful advancement has been the development of standardized, automated dual extraction procedures. The optimized Labcorp extraction processes developed in our CAP/CLIA laboratory in Buffalo, NY, provides a scalable and reproducible solution for processing FFPE tissues. These methods improve nucleic acid yield and quality, reducing the number of quantity not sufficient (QNS) samples and improving sequencing.

Q: Beyond sample processing, how do data analysis guarantee only high-quality variant calls are reported?

A: We have developed stringent quality control (QC) metrics that filter out low-confidence variants and verify that only high-quality data is reported. This minimizes false positives and negatives, providing oncologists with the most reliable insights for patient care.

A key part of our strategy is offering broad genomic solutions—whole-exome sequencing (WES), whole-transcriptome sequencing (WTS) and large targeted panels. They deliver maximum biomarker insights from limited input, detecting small variants, copy number changes and gene fusions with high confidence.

OmniSeq INSIGHT whole exome sequencing validation

OmniSeq INSIGHT whole transcriptome sequencing validation

“With advanced QC tools, we can report high-confidence variant calls, giving biopharma teams the reliable data needed to drive informed decisions,” emphasizes Dr. Newburn.

Q: In summary, what best practices improve CGP outcomes from low-quality or limited samples?

A: Early alignment with an experienced genomics service provider such as Labcorp in sample-constrained workflows is key. By integrating standardized extraction, QC-informed library prep and advanced sequencing platforms, teams can minimize rework, reduce dropout rates and accelerate timelines.

“We've seen cases where only limited nanograms of material have yielded successful sequencing data, enabling both researchers as well as clinicians to obtain high-quality CGP results,” recollects Dr. Newburn.

As CGP becomes further embedded in biopharma research and development, the ability to generate reliable data from limited samples is increasingly critical. Through optimized extraction protocols, scalable NGS workflows and rigorous analytics, Labcorp is helping biopharma partners unlock insights from even the most challenging specimens.

To explore how Labcorp can support your oncology development programs, contact our team.