Teh M T, Tilakaratne W M, Chaplin T, Young B D, Ariyawardana A, Pitiyage G, Lalli A, Stewart J E, Hagi-Pavli E, Cruchley A, Waseem A, Fortune F
Centre for Clinical and Diagnostic Oral Sciences, Barts and The London School of Medicine and Dentistry, Institute of Cell and Molecular Sciences Building, Queen Mary, University of London, London, UK.
J Oral Pathol Med. 2008 Aug;37(7):430-6. doi: 10.1111/j.1600-0714.2008.00643.x. Epub 2008 Feb 17.
Oral submucous fibrosis (OSF) is a high-risk pre-cancerous condition where 7-13% of these patients develop head and neck squamous cell carcinoma (HNSCC). To date there is no cancer predictive markers for OSF patients. Genomic instability hallmarks early genetic events during malignant transformation causing loss of heterozygosity (LOH) and chromosomal copy number abnormality. However, to date there is no study on genomic instability in OSF. Although this condition is known as a high-risk pre-cancerous condition, there is no data regarding the genomic status of this disease in terms of genetic susceptibility to malignant transformation.
In this study, we investigated the existence of genetic signatures for carcinogenesis in OSF. We employed the high-resolution genome-wide Affymetrix Mapping single nucleotide polymorphism microarray technique to 'fingerprint' global genomic instability in the form of LOH in 15 patient-matched OSF-blood genomic DNA samples.
This rapid high-resolution mapping technique has revealed for the first time that a small number of discrete hot-spot LOH loci appeared in 47-53% of the OSF tissues studied. Many of these LOH loci were previously identified regions of genomic instability associated with carcinogenesis of the HNSCC.
To our knowledge, this is the first evidence that genomic instability in the form of LOH is present in OSF. We hypothesize that the genomic instability detected in OSF may play an important role in malignant transformation. Further functional association studies on these putative genes may reveal potential predictive oral cancer markers for OSF patients.
口腔黏膜下纤维化（OSF）是一种高风险的癌前病变，其中7%-13%的患者会发展为头颈部鳞状细胞癌（HNSCC）。迄今为止，尚无针对OSF患者的癌症预测标志物。基因组不稳定性是恶性转化过程中早期遗传事件的标志，可导致杂合性缺失（LOH）和染色体拷贝数异常。然而，迄今为止，尚无关于OSF基因组不稳定性的研究。尽管这种情况被认为是一种高风险的癌前病变，但就其对恶性转化的遗传易感性而言，尚无关于该疾病基因组状态的数据。
在本研究中，我们调查了OSF中致癌的遗传特征的存在情况。我们采用高分辨率全基因组Affymetrix Mapping单核苷酸多态性微阵列技术，以LOH的形式对15例患者匹配的OSF-血液基因组DNA样本中的全球基因组不稳定性进行“指纹识别”。
这种快速的高分辨率映射技术首次揭示，在47%-53%的研究的OSF组织中出现了少量离散的热点LOH位点。其中许多LOH位点是先前确定的与HNSCC致癌作用相关的基因组不稳定区域。
据我们所知，这是首次有证据表明OSF中存在以LOH形式的基因组不稳定性。我们假设在OSF中检测到的基因组不稳定性可能在恶性转化中起重要作用。对这些推定基因进行进一步的功能关联研究可能会揭示OSF患者潜在的口腔癌预测标志物。
