Objectives Genomic and downstream signaling data informing tumor angiogenesis, DNA repair, and immunologic tolerance are required to develop targeted therapy against cervical cancer. The Cervical Cancer Genome Atlas (TCGA) is derived primarily from pre-invasive and early-stage disease, with under-representation of recurrent/metastatic specimens. NRG/GOG-0240 is the phase 3 randomized trial that demonstrated a survival benefit with anti-angiogenesis therapy. Patients enrolled on this study provided tumor samples for whole genome sequencing and whole exome sequencing (to be performed at the New York Genomic Center (NYGC)), as well as RNA-seq and microRNA-seq (University of North Carolina (UNC)), and bioinformatics modeling (Roswell Park Cancer Institute). To determine the feasibility of DNA/RNA extraction from these relatively small, formalin-fixed paraffin-embedded (FFPE) specimens, we conducted a pilot study.
Methods Following pathology review at the NRG Biospecimen Bank at Nationwide Children’s Hospital, DNA/RNA were co-extracted using established protocols. All samples were required to contain at least 50% tumor content for somatic mutation detection.
Results Forty-four out of 107 FFPE samples (41%) underwent successful extraction. 36 were sent in the pilot study including 27 (75%) squamous-cell and 9 (25%) adenocarcinomas. Prior to transfer to NYGC, most samples were noted to have high genomic quality number with few having lower than 10,000 base pairs. Two were flagged for low quality secondary to degradation. One out of 36 samples sent to UNC did not provide sufficient RNA. Five samples were high risk for low DV200 (RNA fragment sizes < 200 base pairs).
Conclusions DNA/RNA extraction can be performed using recurrent/metastatic cervical cancer FFPE specimens.
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