Chromosomal Alterations and Gene Expression Changes Associated with the Progression of Leukoplakia to Advanced Gingivobuccal Cancer.
Chromosomal Alterations and Gene Expression Changes Associated with the Progression of Leukoplakia to Advanced Gingivobuccal Cancer.
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DOI：
10.1016/j.tranon.2017.03.008
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发表时间：
2017-06
影响因子：
5
通讯作者：
Mahimkar MB
中科院分区：
文献类型：
--
作者：
Bhosale PG;Cristea S;Ambatipudi S;Desai RS;Kumar R;Patil A;Kane S;Borges AM;Schäffer AA;Beerenwinkel N;Mahimkar MB
我们提出了一个整合的全基因组分析，可用于预测的风险，从白斑发展为口腔鳞状细胞癌（OSCC）所产生的牙龈颊复合体（GBC）。我们发现白斑的基因组和转录组学特征类似于在OSCC后期观察到的那些，并且几个变化与这种进展相关，包括8q24.3的扩增、8p23.2的缺失以及DERL 3、EIF 5A2、ECT 2、HOXC 9、HOXC 13、MAL、MFAP 5和NELL2的失调。比较原发性肿瘤伴和不伴淋巴结转移的拷贝数谱，我们确定了与转移相关的改变，包括3p26.3、8q24.21、11q22.1、11q22.3的扩增和8p23.2的缺失。综合分析揭示了一些在以前的OSCC研究中从未或很少报道的生物标志物，包括1p36.33（归因于MXRA8），3q26.31（EIF5A2），9p24.1（CD274）和12q13.2（HOXC 9和HOXC 13）的扩增。此外，我们发现1p36.33和11q22.1的扩增与不良的临床结果密切相关。总的来说，我们的研究结果描绘了基因组的变化，可用于治疗管理潜在的恶性白斑和口腔鳞癌患者的淋巴结转移的风险较高。
We present an integrative genome-wide analysis that can be used to predict the risk of progression from leukoplakia to oral squamous cell carcinoma (OSCC) arising in the gingivobuccal complex (GBC). We find that the genomic and transcriptomic profiles of leukoplakia resemble those observed in later stages of OSCC and that several changes are associated with this progression, including amplification of 8q24.3, deletion of 8p23.2, and dysregulation of DERL3, EIF5A2, ECT2, HOXC9, HOXC13, MAL, MFAP5 and NELL2. Comparing copy number profiles of primary tumors with and without lymph-node metastasis, we identify alterations associated with metastasis, including amplifications of 3p26.3, 8q24.21, 11q22.1, 11q22.3 and deletion of 8p23.2. Integrative analysis reveals several biomarkers that have never or rarely been reported in previous OSCC studies, including amplifications of 1p36.33 (attributable to MXRA8), 3q26.31 (EIF5A2), 9p24.1 (CD274), and 12q13.2 (HOXC9 and HOXC13). Additionally, we find that amplifications of 1p36.33 and 11q22.1 are strongly correlated with poor clinical outcome. Overall, our findings delineate genomic changes that can be used in treatment management for patients with potentially malignant leukoplakia and OSCC patients with higher risk of lymph-node metastasis.