Century-old archived tissue samples still yield measurable human DNA

Formalin-fixed, paraffin-embedded (FFPE) tissue archives hold promise for genomic research because they can link genetic data to long-term clinical and historical records. Yet the chemistry that preserves these samples also fractures their DNA, and researchers have questioned whether tissue stored for many decades could yield genetic material suitable for modern analysis. A study of archived specimens from Strasbourg and Geneva, published in BMC Genomics, now offers a carefully quantified answer: much of this century-old material still contains recoverable human DNA, provided the fixation was favorable and the extraction method is up to the task.

The study examined two cohorts of FFPE tissue blocks. The first comprised 79 blocks collected and archived in 1973 in the Strasbourg Pathological Tissue Archive (SPTA). The second came from the Geneva Brain Bank (GBB) and consisted of 51 blocks collected between 1928 and 1971, meaning some specimens had spent nearly a century embedded in paraffin wax under conservation conditions that varied considerably over the decades.

To assess what remained inside these blocks, the team used a forensic-grade quantitative PCR (qPCR) assay, running the QIAGEN Investigator Quantiplex Pro Kit on a Rotor-Gene Q instrument. This approach goes beyond simply asking whether DNA is present. It measures the concentration of human DNA, distinguishes short from longer DNA fragments, assesses the degree of degradation, and detects substances that might inhibit the PCR reaction itself.

The results reveal a consistent pattern of fragmentation. A high proportion of the samples yielded human DNA fragments of 80 base pairs and 95 base pairs, while very few produced fragments as long as 205 base pairs. The DNA preserved in these archives is short and broken, exactly what decades of formalin fixation and storage would be expected to produce. That constraint has a direct consequence for how this material can be studied: the authors state that future analyses will need to rely on next-generation sequencing (NGS) technologies and approaches designed to work with short fragments.

Fixation chemistry emerged as a critical variable. All twelve organ samples that had been treated with Bouin’s solution gave poor results. In contrast, among the 117 samples fixed in formalin, 58.1 percent showed more than 0.25 nanograms per microliter of 80 base pair human DNA fragments, and 37.6 percent exceeded 1 nanogram per microliter.

The comparison between fixation and storage time is one of the more intriguing aspects of the dataset. The samples spanned nearly a century of archival history, yet the variation in DNA recovery appeared to be more strongly associated with how the tissue was fixed than with how long it had been stored. The authors frame this as an observation from their dataset, noting that further controlled analyses will be needed to disentangle these influences, since the archival conditions were not standardized and the two cohorts differed in provenance and handling.

Methodologically, the study took what the researchers describe as a discovery approach. Rather than imposing a uniform sampling protocol, sampling and extraction techniques were dictated by the material constraints of each archive, while a single common quantification method was applied across all samples. This design reflects the reality of working with historical collections, where block size, tissue type, and preservation history vary unpredictably, and it demonstrates that automated extraction methods optimized for FFPE material can recover usable DNA even from samples kept under inconsistent conservation conditions.

The study’s cautionary notes deserve emphasis. The fragmented nature of the recovered DNA was an expected result, and the authors stress that quantification is a first step rather than a demonstration of full genomic analysis. Short fragments limit which sequencing strategies and analytical approaches are feasible, and the observed association between fixation conditions and DNA recovery remains provisional pending controlled comparisons.

Even so, the message for archivists and genomicists alike is one of cautious optimism: the genetic contents of century-old tissue collections are not necessarily lost, and with forensic-grade quantification and NGS-based methods, a meaningful share of this material may yet contribute to retrospective genomic research.

Subject of Research: Quantification of human DNA in century-old FFPE tissue archives for retrospective genomic studies

Article Title: Quantification of human DNA from century-old archived FFPE samples for retrospective genomic studies

Article References: Zvenigorosky, V., Gonzalez, A., Broisin, L., Fausser, J.-L., Jeanjean, N., Hluszko Pontet, A., Cannet, C., Lamy, C., Keyser, C., & Bonah, C. (2026). Quantification of human DNA from century-old archived FFPE samples for retrospective genomic studies. BMC Genomics. https://doi.org/10.1186/s12864-026-13375-6

Image Credits: AI Generated

DOI: 10.1186/s12864-026-13375-6

Keywords: FFPE tissue, archived samples, DNA quantification, qPCR, forensic genetics, DNA degradation, Geneva Brain Bank, Strasbourg Pathological Tissue Archive, next-generation sequencing, retrospective genomic studies, fixation chemistry, Quantification