Loss of heterozygosity at chromosome arms 3p, 9p, 11q and 17p are well-established oncogenetic aberrations in oral precancerous lesions and promising biomarkers to monitor the development of oral cancer. Non-invasive LOH screening of brushed oral cells is a preferable method for precancer detection in patients at increased risk for head and neck squamous cell carcinoma (HNSCC) such as Fanconi anemia (FA) patients. We determined the prevalence of LOH in brushed samples of the oral epithelium of 141 FA patients and 144 aged subjects, and studied the association between LOH and HNSCC. LOH was present in 14 (9.9%) non-transplanted FA patients, whereas no LOH was detected in a low risk group (n=50, >58 years, non-smoking/non-alcohol history) and a group with somewhat increased HNSCC risk (n=94, >58 years, heavy smoking/excessive alcohol use); Fisher's exact test p=0.023 and p=0.001, respectively. Most frequent genetic alteration was LOH at 9p. Age was a significant predictor of LOH (OR 1.13, p=0.001). Five FA patients developed HNSCC during the study at a median age of 39.6 years (range 24.8-53.7). LOH was significantly associated with HNSCC (Fisher's exact test p=0.000). Unexpectedly, the LOH assay could not be used for transplanted FA patients since donor DNA in brushed oral epithelium, most likely from donor leukocytes present in the oral cavity, disturbed analysis. Non-invasive screening using a LOH assay on brushed samples of the oral epithelium has a promising outlook in FA patients. However, assays need to be adapted in case of stem cell transplantation, because of contaminating donor DNA.
- Received June 3, 2015.
- Revision received August 3, 2015.
- Accepted August 5, 2015.
- Copyright © 2015, American Association for Cancer Research.