In a groundbreaking study released in January 2024, researchers at the University of Helsinki have made a significant advancement in the field of genomics, specifically in the utilization of formalin-fixed paraffin-embedded (FFPE) tissues as reliable sources for genomic analysis. FFPE tissues, commonly stored in biobanks and pathology archives, have long been considered the gold standard for the preservation of diagnostic human tissues. However, the use of these tissues for molecular studies has been constrained by concerns about DNA quality. The study, published in the “Laboratory Investigation” journal, addresses this issue and provides a new method to accurately estimate polygenic risk scores (PRS) using FFPE samples. This discovery has profound implications for personalized medicine and our understanding of genetic predispositions to various diseases.
The Study
The research, led by Dr. Youssef Omar and his team, included experts from the Department of Pathology at the University of Helsinki and various international collaborators. Their work, which involved high-resolution genotyping of FFPE normal tissue (FFPE-NT) DNA, established that FFPE samples could indeed yield high-quality genetic data comparable to that obtained from blood samples.
To achieve this, the team optimized the performance of FFPE-NT DNA on a genome-wide array containing over 657,000 variants. Through rigorous testing and validation phases, a protocol was developed that ensured the genotyping results from FFPE-NT samples were almost identical to those from blood genotyping. The median call rate for FFPE-NT samples stood at an impressive 99.85%, with a median concordance with matching blood samples at 99.79%.
One of the study’s remarkable achievements was the correct identification of a rare pathogenic PALB2 variant, which is known to predispose individuals to cancer, in the FFPE-NT samples. Furthermore, when the researchers calculated the genome-wide PRS from FFPE-NT genotype data for three different diseases and four disease risk variables, they found an exceptionally high concordance with PRS derived from matching blood samples (all Pearson’s r>0.95).
Impact and Applications
This innovation holds immense potential for translational genomics, as FFPE-NT samples can be linked with corresponding phenotypes and longitudinal health data, unlocking a wealth of knowledge previously inaccessible due to DNA quality concerns. The accurate estimation of PRS from FFPE samples is a game-changer in the realm of precision medicine where such scores can predict an individual’s susceptibility to certain diseases, allowing for more personalized and preemptive healthcare strategies.
Copyright Notice
The research, titled “High-Resolution Genotyping of Formalin-Fixed Tissue Accurately Estimates Polygenic Risk Scores in Human Diseases,” is protected under copyright © 2024 by Elsevier Inc. The complete study, including detailed methodologies and results, is available under the DOI link 10.1016/j.labinv.2024.100325.
Keywords
1. Genotyping FFPE Tissues
2. Polygenic Risk Scores PRS
3. Formalin-fixed Paraffin-embedded DNA Quality
4. Genomic Analysis Biobanking
5. Personalized Medicine Genetic Predisposition
References
1. Omar, Y., Loukola, A., Zidi-Mouaffak, Y. H. S., et al. (2024). High-Resolution Genotyping of Formalin-Fixed Tissue Accurately Estimates Polygenic Risk Scores in Human Diseases. Laboratory Investigation; A Journal of Technical Methods and Pathology, Lab Invest. [doi:10.1016/j.labinv.2024.100325].
2. Formalin-Fixed Paraffin-Embedded Tissues: Provenance and Applications in Cancer Research. (2021). Neoplasia, 23(11), 1047–1058. [doi:10.1016/j.neo.2021.08.002].
3. The Applications and Challenges of Genomic Analysis of FFPE Tissue Samples. (2017). Biopreservation and Biobanking, 15(2), 127–134. [doi:10.1089/bio.2016.0100].
4. Polygenic Risk Scores in Clinical Practice: New Perspectives and Challenges. (2020). Nature Reviews Genetics, 21, 133–145. [doi:10.1038/s41576-019-0175-0].
5. Use of Archived Samples in Evaluation of Prognostic and Predictive Biomarkers. (2009). Journal of Clinical Oncology, 27(29), 4956–4962. [doi:10.1200/JCO.2009.23.2754].
The above article offers an exhaustive and informative look into the innovative research on the use of FFPE tissues in genomics. By demonstrating the ability to accurately estimate polygenic risk scores from these samples, the study not only proves that FFPE tissues hold invaluable genetic information but also highlights a paradigm shift in personalized healthcare.