Divergent routes to oral cancer
Divergent routes to oral cancer
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DOI：
10.1158/0008-5472.can-06-0186
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发表时间：
2006-08-01
期刊：
影响因子：
11.2
通讯作者：
Harrison, Paul R.
中科院分区：
文献类型：
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作者：
Hunter, Keith D.;Thurlow, Johanna K.;Harrison, Paul R.
头颈部鳞状细胞癌（HNSCC）患者多为晚期肿瘤，治疗困难，因此早期诊断高危癌前病变和早期癌非常重要。HNSCC目前被认为是一种单一的进展机制，导致永生的浸润性癌症。然而，我们已经发现，近似40%的原发性口腔SCC在培养中是致命的，并且这些具有更好的预后。约60%的口腔癌前病变（发育不良）也是致命的。根据p53突变和p16（INK4A）表达缺失判断，致死性和永生性肿瘤是在体内产生的，而p16（INK4A）表达缺失仅见于永生性培养物来源的原始肿瘤中。为了研究异型增生与SCC的关系，我们对4例正常口腔粘膜活检、19例异型增生和16例SCC的原代培养物进行了微阵列分析。谱聚类使用奇异值分解和其他生物信息学技术表明，发展的致命和不朽的SCC涉及不同的转录变化。这两种SCC类型共享在其各自发育不良中发现的大部分转录变化，但具有额外的变化。此外，随后进展为SCC的高危发育不良比非进展性发育不良更接近SCC。这首次表明，口腔鳞状细胞癌通过中间发育不良的发展有不同的致命和不朽的途径。我们相信，这一新的信息可能会导致新的方法来分类HNSCC的预后。
Most head and neck squamous cell carcinoma (HNSCC) patients present with late-stage cancers, which are difficult to treat. Therefore, early diagnosis of high-risk premalignant lesions and incipient cancers is important. HNSCC is currently perceived as a single progression mechanism, resulting in immortal invasive cancers. However, we have found that similar to 40% of primary oral SCCs are mortal in culture, and these have a better prognosis. About 60% of oral premalignancies (dysplasias) are also mortal. The mortal and immortal tumors are generated in vivo as judged by p53 mutations and loss of p16(INK4A) expression being found only in the original tumors from which the immortal cultures were derived. To investigate the relationships of dysplasias to SCCs, we did microarray analysis of primary cultures of 4 normal oral mucosa biopsies, 19 dysplasias, and 16 SCCs. Spectral clustering using the singular value decomposition and other bioinformatic techniques showed that development of mortal and immortal SCCs involves distinct transcriptional changes. Both SCC classes share most of the transcriptional changes found in their respective dysplasias but have additional changes. Moreover, high-risk dysplasias that subsequently progress to SCCs more closely resemble SCCs than nonprogressing dysplasias. This indicates for the first time that there are divergent mortal and immortal pathways for oral SCC development via intermediate dysplasias. We believe that this new information may lead to new ways of classifying HNSCC in relation to prognosis.