Abstract：
Oral leukoplakia (OL) and oral submucosal fibrosis (OSMF) are precancerous conditions with common etiologies but with different risks for oral cancer (OC) progression. In rare cases, both conditions occur in the same patient and provide an opportunity for understanding the common and distinctive variants upon exposure of genetically identical normal cells to the same carcinogen(s). We performed exome sequencing of a patient with OL (hyperplasia, but no dysplasia) and OSMF (grade II) in the opposite cheeks using blood DNA as the reference genome. The overall somatic variant burden was higher in OSMF than OL, but opposite in the case of copy number alterations. OL-specific variants were enriched in genes associated with DNA repair, cell division/cell cycle checkpoint pathways, whereas in OSMF, extracellular matrix-receptor interaction was mainly affected. The proportions of variants in cancer driver genes and cancer driver mutations were similar in both cases indicating no difference in the potential risk associated with the two conditions at the stages sampled. Future studies on rare cases similar to the one described in this report will help in understanding the molecular basis of differences associated with OL and OSMF and shared processes accompanying OC progression.
摘要：
口腔白斑（OL）和口腔粘膜下纤维化（OSMF）是癌前疾病，具有共同的病因，但口腔癌（OC）进展的风险不同。在极少数情况下,这两种情况都发生在同一患者中，并为了解遗传相同的正常细胞暴露于同一致癌物后的常见和独特变异提供了机会。我们对一名患有OL（增生，但没有发育异常）和OSMF（II级）在对面的脸颊使用血液DNA作为参考基因组。OSMF的总体体细胞变异负荷高于OL，但在拷贝数改变的情况下相反。OL特异性变体富含与DNA修复相关的基因，细胞分裂/细胞周期检查点途径，而在OSMF中，细胞外基质-受体相互作用主要受影响。在两种情况下，癌症驱动基因和癌症驱动突变的变异比例相似，表明在采样阶段与两种情况相关的潜在风险没有差异。与本报告中描述的类似的罕见病例的未来研究将有助于理解与OL和OSMF相关的差异的分子基础以及伴随OC进展的共同过程。
