Unveiling STRs instability in a colorectal cancer FFPE sample: a case report

Area of Science:

• Forensic Genetics
• Molecular Biology
• Cancer Research

Background:

• Forensic investigations often rely on formalin-fixed paraffin-embedded (FFPE) tissues when other biological samples are unavailable.
• Tumor tissues frequently exhibit microsatellite instability (MSI) and loss of heterozygosity (LOH), which can alter genetic profiles.
• These genetic alterations in tumor samples can complicate accurate individual identification and paternity testing.

Purpose of the Study:

• To investigate the impact of genomic instability in FFPE tumor tissue on DNA profiling for forensic applications.
• To compare genetic profiles from cancerous FFPE tissue with those from normal FFPE tissue from the same individual.

Main Methods:

• DNA extraction from two FFPE samples: one colorectal cancer tissue and one normal tissue from the same male subject.
• Microsatellite analysis to compare genetic profiles between the tumor and normal tissue samples.
• Assessment of genomic alterations including MSI, LOH, and duplication events.

Main Results:

• The tumor tissue sample exhibited three instances of genomic instability affecting autosomal loci (FGA, CSF1P0, D21S2055).
• A duplication phenomenon was observed at the DYS438 locus in the tumor tissue.
• The genetic profile derived from the tumor tissue was distorted due to MSI/LOH, creating a fictitious profile.

Conclusions:

• FFPE tumor tissue with MSI/LOH can generate inaccurate genetic profiles, compromising forensic identification.
• Comparing tumor FFPE DNA profiles with normal FFPE DNA profiles is crucial for accurate forensic genetic analysis.
• The study highlights the challenges and potential pitfalls of using FFPE tumor samples in forensic genetics.