# Advanced Omics and Radiobiological Tissue Archives: The Future in the Past
## 4 Omics Analysis on FFPE Samples in Radiobiological Archives
### Genomics and Transcriptomics
The study identified mutations in FGFR3 and FGFR4 in the recurrent tumour compared with the treatment-naive tumour [104]. To investigate the association between tumour genetic profiles and radiotherapy outcome, [PERSON] et al. performed exon sequencing on cancer-related genes in FFPE samples obtained from UCC patients following radiotherapy [105]. The analysis identified the mutations in the intracellular tyrosine kinase domain of the FGFR gene family. The observations were compared with data generated on FFPE and fresh-frozen samples in previously published data where PIK3 CA was often identified as a marker. The authors argued that a low association of prognosis with PIK3 CA is related to the tumour type treatment. The authors also found worse 5-year progression-free survival (PFS) for FGFR mutation-positive patients, suggesting a potential role for the FGFR signalling pathway in UCC radioresistance [105]. In comparison to mRNA, miRNAs in FFPE tissues were shown to be more robust to degradation, partially due to their smaller size. miRNAs are known to contribute to the radiation response in several cancers [106, 107, 108, 109]. [PERSON] et al. compared miRNA isolated from FFPE tumour samples of breast cancer patients with and without local relapse using a microarray to identify the radioresistance associated miRNA [107]. The analysis identified 11 miRNAs significantly differentially expressed between the two groups. Among them, overexpressed miR-139-5p was selected for further validation. The authors showed that the miR-139-5p and its targets were strong predictive biomarkers for radiation sensitivity in vitro and correlated with outcomes in radiotherapy-treated patients in breast cancer cohorts [107]. To identify the miRNAs signature for radioresponse of laryngeal squamous cell carcinoma (LSCC), [PERSON] et al. analysed the expression pattern of miRNAs in radioresistancet and radiosensitive tumours of LSCC patients treated with primary radiation therapy [110]. This analysis and validation of additional samples indicated that the expression level of miR-296-5p was associated with radioresistance and recurrence properties of early-stage laryngeal cancer [110]. In contrast to studies performed to identify the radioresistance profile of the tumour, there are only a few studies that investigate the mechanism of radiation-induced cancer using FFPE samples available in radiation archives. Using array comparative genomic hybridization (aCGH), [PERSON] et al. analysed the genomic copy number of radiation-associated papillary thyroid carcinoma in FFPE tissues of the Ukrainian-American cohort [111]. The study identified a significant association between single-copy number alterations (CNAs) and clinical parameters and patient data, including individual gender and radiation dose [111]. [PERSON] et al. analysed the genomic copy number signature associated with radiation exposure in post-Chernobyl breast cancer [112]. The authors compared FFPE tumoursobtained from exposed female Chernobyl clean-up workers and evacuees and matched non-exposed control patients by aCGH. The analysis revealed a significant association of a set of nine signatures of RNAs with radiation exposure but not with any clinical characteristics of the patients and radiation dose [112]. Unlike cancer, not many studies have analysed RNA or miRNA from FFPE lung or heart to investigate the negative effect of radiation exposure on normal tissue. The levels of miR-21 and miR-146a as potential biomarkers of heart disease were measured using FFPE heart tissues in the proteomic study on Mayak autopsies [93]. The analysis showed significant upregulation of both miRNAs in the highest dose group compared to the control and lower dose groups [93].