Germline NGS tests using FFPE samples

The Takeaway: Germline next generation sequencing (NGS) is a powerful tool for unraveling the complex makeup of an individual's genomic makeup. Utilizing formalin-fixed, paraffin-embedded (FFPE) samples has become increasingly valuable in this context, enabling researchers to extract valuable genetic information from archived tissues. This article explores the fascinating intersection of germline NGS tests and FFPE samples, shedding light on their applications, challenges, and the transformative impact they have on personalized medicine.

What are germline NGS tests?

Germline NGS tests are instrumental in identifying genetic mutations associated with germline disorders, allowing for a deeper understanding of an individual's predisposition or genetic cause of certain diseases. Unlike traditional sequencing methods, NGS enables the parallel sequencing of millions of DNA fragments, with potential to provide comprehensive analysis of the entire genome. This high-throughput approach is particularly advantageous for detecting mutations in multiple genes simultaneously, making it an invaluable tool for germline testing.

What are FFPE samples?

Formalin-fixed paraffin-embedded (FFPE) samples are made from tissue sections preserved using formaldehyde and embedded in paraffin wax, which ensures long-term stability. This method is commonly used for pathological examinations and to archive tissues. The use of FFPE samples in germline NGS testing opens up a wealth of opportunities to explore historical genetic data, making it possible to retrospectively analyze genetic changes in diseases over time.

What are some applications of germline NGS tests with FFPE samples?

Cancer genetics: FFPE samples are frequently obtained from cancer tissues, and germline NGS tests allow for the identification of mutations associated with an inherited increased risk of certain cancers. Understanding the germline component of cancer is crucial for developing personalized treatment plans and implementing preventive measures for at-risk individuals.

Historical genetic epidemiology: Historic epidemiology is the study of how disease control efforts have changed disease patterns and transmission over time. By analyzing FFPE samples collected over the years, researchers can trace the evolution of genetic mutations and their prevalence in populations. This retrospective approach provides insights into the changing landscape of germline diseases and may inform public health strategies. These studies can be facilitated by tools like IDT’s xGen™ whole genome sequencing solutions.

Challenges and considerations when using germline NGS tests and FFPE samples

While the combination of germline NGS tests and FFPE samples holds great promise, there are inherent challenges that researchers and clinicians must navigate:

DNA quality and integrity: FFPE samples are often characterized by degraded and fragmented DNA due to the fixation and embedding process. Specialized protocols and technologies are required to extract high-quality DNA for accurate NGS analysis.

Future directions and implications of germline NGS testes and FFPE samples

As technology continues to advance, overcoming current challenges in germline NGS tests using FFPE samples is on the horizon. The integration of artificial intelligence in bioinformatics and improvements in DNA extraction methods offer exciting prospects for enhancing the reliability and efficiency of these tests.

AI in bioinformatics: AI-driven algorithms can aid in the interpretation of complex genetic data, assisting researchers and clinicians in identifying mutations with greater accuracy.

Machine learning models may also contribute to predicting disease trajectories and treatment responses based on historical genetic data.

Advanced DNA extraction technologies: Ongoing research focuses on developing innovative DNA extraction techniques that can improve the quality and integrity of DNA extracted from FFPE samples. These advancements will address current limitations and contribute to the routine integration of germline NGS tests using FFPE samples.

The convergence of germline NGS tests and FFPE samples represents a paradigm shift in genetic testing, offering a retrospective lens into the historical genetic landscape of diseases. Despite challenges related to DNA quality and sample heterogeneity, the potential for unlocking valuable genetic insights and improving personalized medicine is immense. As technology continues to evolve, the marriage of germline NGS tests and FFPE samples will undoubtedly play a pivotal role in shaping the future of genetic diagnostics and therapeutic interventions.