Department of Otolaryngology-Head & Neck Surgery, Henry Ford Health System, Detroit, MI 48202, USA.
J Oncol. 2012;2012:752860. doi: 10.1155/2012/752860. Epub 2012 Apr 12.
Genetic events specific to the pathogenesis of malignancy can offer clues to the tumorigenesis process. The objective of this study was to identify gene alterations that differentiate tumor and nontumor lesions in squamous head and neck cancer (HNSCC). DNA from 220 primary HNSCC with concurrently present tumor and nontumor lesions from the same patient was interrogated for genomic alterations of loss or gain of copy. Conditional logistic regression dealt with tumor and non-tumor records within a patient. Of 113 genes, 53 had univariate effects (P < 0.01), of which 16 genes remained in the multivariable model with P < 0.01. The model had a C-index (ROC) of 0.93. Loss of CDKN2B and gain of BCL6, FGF3, and PTP4A3 predicted tumor. Loss of BAK1 and CCND1 and gain of STCH predicted nontumor. This highly powered model assigned alterations in 16 genes specific for malignant versus nonmalignant lesions, supporting their contribution to the pathogenesis of HNSCC as well as their potential utility as relevant targets for further evaluation as markers of early detection and progression.
特定于恶性肿瘤发病机制的遗传事件可以为肿瘤发生过程提供线索。本研究的目的是鉴定区分头颈部鳞状细胞癌（HNSCC）肿瘤和非肿瘤病变的基因改变。对 220 例伴有同一患者肿瘤和非肿瘤病变的原发性 HNSCC 的 DNA 进行了基因组拷贝缺失或增益改变的检测。条件逻辑回归处理了患者内的肿瘤和非肿瘤记录。在 113 个基因中，有 53 个具有单变量效应（P<0.01），其中 16 个基因在多变量模型中仍然具有 P<0.01 的效应。该模型的 C 指数（ROC）为 0.93。CDKN2B 的缺失和 BCL6、FGF3 和 PTP4A3 的获得提示肿瘤。BAK1 和 CCND1 的缺失和 STCH 的获得提示非肿瘤。该高功效模型鉴定了 16 个基因的改变，这些改变对恶性和非恶性病变具有特异性，支持它们对 HNSCC 发病机制的贡献，以及它们作为早期检测和进展相关标志物的进一步评估的潜在用途。
