Wiseman Sam M, Stoler Daniel L, Anderson Garth R
Department of Surgical Oncology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA.
Surg Oncol Clin N Am. 2004 Jan;13(1):1-11. doi: 10.1016/S1055-3207(03)00118-2.
Measurements of genomic instability, or identification of genes responsible for instability, may potentially be used as molecular markers to predict disease course and response to therapy. Other possible applications include use of genomic instability measurements, or genes, as tools to screen for primary or recurrent disease. Methodologies for detection of genetic mutations in saliva, blood, and sputum have already been described[61,62]. Brennan et al [63] have described a molecular technique for analyzing histopathologically negative margins and lymph nodes for the presence of p53 gene mutation. This study showed that a positive molecular margin significantly predicted disease recurrence. The recognition that HNSCC is a genetically heterogeneous disease represents a major step toward developing an understanding of its underlying genetic basis. To develop an insight into this genetically heterogeneous disease, investigators must not only focus their efforts on specific head and neck disease sites. Laser-capture microdissection represents a powerful tool for isolating very specific cell populations from tumors [64]. Leethanakul et al[65] performed laser-capture microdissection on oral cavity SCC to construct stage-specific cDNA libraries. Sequencing of 96 clones from each of the six libraries constructed suggested the existence of 132 novel genes, which may play a role in the pathogenesis of HNSCC. The current literature suggests that many individuals diagnosed withHNSCC are genetically predisposed to developing malignancy because of some inherent deficiency of their capacity to maintain their genome in the presence of environmental stressors. Head and neck cancers are highly heterogeneous tumors and exhibit a wide variety of forms of genomic instability. Thus, genomic instability may be viewed as a fundamental force driving head and neck tumorigenesis and evolution. Future study of the specific genetic mechanisms that underlie genomic instability in the HNSCCpatient population is needed. It is only through study of this fundamental force that drives the development of these tumors that clinicians may gain the insight required to develop new diagnostic and therapeutic modalities to benefit the HNSCC patient population as a whole.
基因组不稳定性的测量，或对导致不稳定性的基因的鉴定，有可能被用作分子标记来预测疾病进程和对治疗的反应。其他可能的应用包括使用基因组不稳定性测量或基因作为筛查原发性或复发性疾病的工具。检测唾液、血液和痰液中基因突变的方法已经有过描述[61,62]。布伦南等人[63]描述了一种分子技术，用于分析组织病理学检查阴性的切缘和淋巴结中p53基因突变的存在情况。这项研究表明，分子切缘阳性显著预测疾病复发。认识到头颈部鳞状细胞癌是一种基因异质性疾病，是朝着理解其潜在遗传基础迈出的重要一步。为了深入了解这种基因异质性疾病，研究人员不仅必须将精力集中在特定的头颈部疾病部位。激光捕获显微切割是从肿瘤中分离非常特定细胞群体的有力工具[64]。利塔纳库尔等人[65]对口腔鳞状细胞癌进行了激光捕获显微切割，以构建阶段特异性cDNA文库。对构建的六个文库中每个文库的96个克隆进行测序，表明存在132个新基因，这些基因可能在头颈部鳞状细胞癌的发病机制中起作用。目前的文献表明，许多被诊断为头颈部鳞状细胞癌的个体由于在环境应激源存在的情况下维持其基因组的能力存在一些固有缺陷，在遗传上易患恶性肿瘤。头颈部癌症是高度异质性肿瘤，表现出多种形式的基因组不稳定性。因此，基因组不稳定性可被视为驱动头颈部肿瘤发生和演变的基本力量。需要对头颈部鳞状细胞癌患者群体中基因组不稳定性背后的具体遗传机制进行进一步研究。只有通过研究驱动这些肿瘤发展的这种基本力量，临床医生才可能获得开发新的诊断和治疗方法所需的见解，从而使整个头颈部鳞状细胞癌患者群体受益。
