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对晚期口腔癌的基因组分析揭示了 11q 染色体改变作为不良临床结局的标志物。

Genomic profiling of advanced-stage oral cancers reveals chromosome 11q alterations as markers of poor clinical outcome.

机构信息

Tata Memorial Centre, Advanced Centre for Treatment, Research and Education in Cancer, Cancer Research Institute, Navi Mumbai, India.

出版信息

PLoS One. 2011 Feb 28;6(2):e17250. doi: 10.1371/journal.pone.0017250.

Abstract

Identifying oral cancer lesions associated with high risk of relapse and predicting clinical outcome remain challenging questions in clinical practice. Genomic alterations may add prognostic information and indicate biological aggressiveness thereby emphasizing the need for genome-wide profiling of oral cancers. High-resolution array comparative genomic hybridization was performed to delineate the genomic alterations in clinically annotated primary gingivo-buccal complex and tongue cancers (n = 60). The specific genomic alterations so identified were evaluated for their potential clinical relevance. Copy-number changes were observed on chromosomal arms with most frequent gains on 3q (60%), 5p (50%), 7p (50%), 8q (73%), 11q13 (47%), 14q11.2 (47%), and 19p13.3 (58%) and losses on 3p14.2 (55%) and 8p (83%). Univariate statistical analysis with correction for multiple testing revealed chromosomal gain of region 11q22.1-q22.2 and losses of 17p13.3 and 11q23-q25 to be associated with loco-regional recurrence (P = 0.004, P = 0.003, and P = 0.0003) and shorter survival (P = 0.009, P = 0.003, and P 0.0001) respectively. The gain of 11q22 and loss of 11q23-q25 were validated by interphase fluorescent in situ hybridization (I-FISH). This study identifies a tractable number of genomic alterations with few underlying genes that may potentially be utilized as biological markers for prognosis and treatment decisions in oral cancers.

摘要

确定与高复发风险相关的口腔癌病变并预测临床结果仍然是临床实践中的难题。基因组改变可能会提供预后信息并指示生物学侵袭性,从而强调需要对口腔癌进行全基因组分析。进行了高分辨率阵列比较基因组杂交,以描绘临床注释的原发性牙龈 - 颊复合体和舌癌(n = 60)中的基因组改变。评估如此确定的特定基因组改变的潜在临床相关性。在染色体臂上观察到拷贝数变化,最频繁的增益是 3q(60%)、5p(50%)、7p(50%)、8q(73%)、11q13(47%)、14q11.2(47%)和 19p13.3(58%),以及 3p14.2(55%)和 8p(83%)的缺失。经过多次测试校正的单变量统计分析显示,11q22.1-q22.2 区域的染色体增益和 17p13.3 和 11q23-q25 的缺失与局部区域复发(P = 0.004,P = 0.003 和 P = 0.0003)和较短的生存时间(P = 0.009,P = 0.003 和 P 0.0001)相关。11q22 的增益和 11q23-q25 的缺失通过间期荧光原位杂交(I-FISH)得到验证。这项研究确定了少数几个具有潜在基因的可处理的基因组改变,这些改变可能被用作口腔癌预后和治疗决策的生物学标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b092/3046132/36b51d930fa1/pone.0017250.g001.jpg

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