The Role of Genomic Instability in the Development of Human Cancer

摘要: Cancer development is a multi-step process through which cells acquire increasingly abnormal proliferative and invasive behaviors. Furthermore, cancer represents unique form of genetic disease, characterized by the accumulation multiple somatic mutations in population undergoing neoplastic transformation (1–5). Several forms molecular alteration have been described human cancers, including gene amplifications, deletions, insertions, rearrangements, point (5, 6). In many cases specific lesions identified that are associated with and/or tumor progression particular tissue or cell type (4). Statistical analyses age-specific mortality rates for different predict (three to eight) target genes required genesis outgrowth most clinically diagnosable tumors (7). accordance this prediction, it has suggested grow clonal expansion driven mutation (1,2,8–10). model, first leads limited progeny single cell, each subsequent gives rise new greater potential. The idea carcinogenesis supported morphologic observations transitions between premalignant (benign) growths malignant tumors. some systems (such as colon), transition from benign can be easily documented occurs discernible stages, adenoma, carcinoma situ, carcinoma, eventually local distant metastasis (11,12). Moreover, alterations shown correlate these well-defined histopathologic stages (13,14). However, important recognize affected cells, not necessarily order changes accumulate, determines formation progression. These suggest strongly observed cancers represent integral (necessary) components