Genomic Instability Is Frequent in Oral and Rare in Nasal Mucosal Cells of Allogeneic HCT Recipients.

Genomic Instability (GI), appraised by microsatellite length alteration, is a precancerous or cancerous condition. We hypothesized that genomic instability is frequent in oral but not nasal mucosal cells of HCT recipients as oral but not nasal carcinoma is frequent in long-term HCT survivors.We examined epithelial cells from buccal and nasal mucosa of 35 subjects for the presence of GI at 15 microsatellite loci spanning 14 human autosomes. The study population included long-term allo-HCT survivors (4–22 yrs, n=18) and short-term allo-HCT survivors (2–3 months, n=5), and long-term auto-HCT survivors (4–12 yrs, n=5). Controls also included 5 patients treated with intensive chemotherapy and 2 healthy volunteers. DNA extracted from peripheral blood leukocytes and cells of nasal and buccal mucosa was PCR amplified for a panel of 15 Short tandem repeat (STR) markers (ABI-Identifiler _TM). The amplicons were subjected to capillary electrophoresis and fragment size analysis was performed to identify novel allele peaks (one that was absent in donor and recipient blood pre-transplant but present in recipient mucosa post-transplant) indicative of microsatellite instability (MSI). MSI was observed in buccal mucosal cells of 56% long-term survivors of allo-HCT; the number of STR loci showing novel allele peaks ranged from 1–6 (median=3). None of the short-term survivors of allo-HCT, long-term survivors of auto-HCT, or control individuals showed MSI in the buccal mucosal cells. Only one allogeneic HCT survivor showed MSI (at one STR locus) in nasal mucosal cells. No genomic alterations were observed in blood leukocytes of any of the above patients or controls. In conclusion, genomic instability is frequently observed in long-term allo-HCT suvivors in oral mucosal cells but rarely in nasal mucosal cells. The facts that oral but not nasal mucosa is frequently involved in chronic GVHD and that MSI was not detected in recipients of auto-HCT suggest that graft-vs-host reaction induces genomic instability.