Two distinct routes to oral cancer differing in genome instability and risk for cervical node metastasis.
Two distinct routes to oral cancer differing in genome instability and risk for cervical node metastasis.
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DOI：
10.1158/1078-0432.ccr-11-1944
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发表时间：
2011-11-15
期刊：
影响因子：
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通讯作者：
Albertson DG
中科院分区：
文献类型：
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作者：
Bhattacharya A;Roy R;Snijders AM;Hamilton G;Paquette J;Tokuyasu T;Bengtsson H;Jordan RC;Olshen AB;Pinkel D;Schmidt BL;Albertson DG
口腔癌或癌前病变的处理问题包括识别有转移、肿瘤复发和第二原发癌风险的患者，或癌前病变(异型增生)进展为癌症的风险。因此，这项研究的目的是阐明基因组异常在口腔癌进展和转移中的作用。用阵列比较基因组杂交(CGH)技术检测口腔异型增生和鳞癌组织中拷贝数改变的谱。研究了与临床特征的相关性，并在独立的队列中证实了结果。一个或多个染色体异常+3q24-qTER、-8pert-p23.1、+8q12-q24.2和+20的存在区分了一个主要亚组(70%-80%的病变，称为3q8pq20亚型)和其余的(20%-30%的病变，非3q8pq20)。在大多数染色体不稳定的肿瘤中，3q8pq20亚型与染色体不稳定和差异甲基化有关。在两个独立的口腔鳞状细胞癌队列中，这两种亚型的临床结果显著不同，颈(颈)淋巴结转移的风险几乎完全与3q8pq20亚型相关。两种不同亚型的口腔病变在染色体不稳定性和转移风险方面存在差异，表明+3q、-8p、+8q和+20是一种具有临床实用价值的生物标志物，可用于识别有转移风险的患者。此外，虽然基因组改变的数量增加可能是癌症进展的先兆，但缺乏拷贝数变化的发育不良病变不能被认为是良性的，因为它们是非3q8pq20局部侵袭性的潜在先兆，但不是转移性口腔鳞癌。
Problems in management of oral cancers or pre-cancers include identification of patients at risk for metastasis, tumor recurrence, and second primary tumors, or risk for progression of pre-cancers (dysplasia) to cancer. Thus, the objective of this study was to clarify the role of genomic aberrations in oral cancer progression and metastasis. The spectrum of copy number alterations in oral dysplasia and SCC was determined by array comparative genomic hybridization (CGH). Associations with clinical characteristics were studied and results confirmed in an independent cohort. The presence of one or more of the chromosomal aberrations +3q24-qter, -8pter-p23.1, +8q12-q24.2 and +20 distinguishes a major subgroup (70-80% of lesions, termed 3q8pq20 subtype) from the remainder (20-30% of lesions, non-3q8pq20). The 3q8pq20 subtype is associated with chromosomal instability and differential methylation in the most chromosomally unstable tumors. The two subtypes differ significantly in clinical outcome with risk for cervical (neck) lymph node metastasis almost exclusively associated with the 3q8pq20 subtype in two independent oral SCC cohorts. Two subtypes of oral lesions indicative of at least two pathways for oral cancer development were distinguished that differ in chromosomal instability and risk for metastasis, suggesting that +3q, -8p, +8q and +20 constitute a biomarker with clinical utility for identifying patients at risk for metastasis. Moreover, while increased numbers of genomic alterations can be harbingers of progression to cancer, dysplastic lesions lacking copy number changes cannot be considered benign as they are potential precursors to non-3q8pq20 locally invasive, yet not metastatic oral SCC.