- 期刊
乳癌的分子生物學與分子遺傳學
Molecular Genetics of Breast Tumorigenesis
摘要
乳癌的發生具有高度的異質性，雖然臨床上有些指標被拿來作為癌症不同階段的代表，但是個案間與癌症組織細胞間的特性，卻不盡相同。這些現象均促使乳癌研究學者希望以分子機轉來解釋臨床與病理上所觀察到的複雜現象。根據遺傳性乳癌的致病基因，包括p53、ATM、BRCA1、BRCA2，均是參與細胞DNA雙股螺旋鏈斷裂修補的機制，許多研究均特別著重此一機制與乳癌生成的關係。另一方面，因為許多癌症相關基因對細胞基本功能的維持，均扮演關鍵必要的角色，所以這些基因功能的缺損，會引起極嚴重的後果與細胞的死亡，反而不利癌症生成，因此基因較輕微的變異，反而與癌症的相關性較強，所以過去許多基於癌症相關機轉，所進行的候選基因研究以及近來的全基因體掃瞄，均指出許多基因多型態性的共同影響對乳癌生成的重要性。
並列摘要
Breast cancer is considered to display a high degree of intratumor heterogeneity, without any obvious morphologically and pathologically steps to define sequential evolution, and its progression may vary among individual tumors. In an attempt to elucidate these etiological and phenotypic complexities, scientific community, based on the fundamental concept that genomic instability is the engine of both tumor progression and tumor heterogeneity, tests the hypothesis that breast cancer pathogenesis is driven by double-strand-break-initiated chromosome instability. The rationale underlying this hypothesis is derived from the clues provided by family breast cancer syndromes, in which susceptibility genes, including p53, ATM, BRCA1 and BRCA2, are involved within the common functional pathway of DSB-related checkpoint/repair. On the other hand, it is possible that, since many cancer-associated genes are so crucial for mammalian cells to maintain cellular viability and genomic stability, any severe defects in them would result in serious outcomes and block of subsequent cell outgrowth and tumor formation. Thus, only subtle defects arising from low-penetrance alleles would escape lethality accumulating essential genetic changes, and be associated with cancer formation. Candidate-gene-based studies and recent genome-wide association studies have identified genotypic polymorphisms of many genes, which jointly contribute the formation of breast cancer development.