Clonality of basal cell carcinoma--molecular analysis of an interesting case.
Clonality of basal cell carcinoma--molecular analysis of an interesting case.
复制标题
基底细胞癌的克隆性——一个有趣病例的分子分析。
DOI：
10.1111/1523-1747.ep12344982
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Peacocke,M
中科院分区：
文献类型：
--
作者：
Walsh,DS;Tsou,HC;Harrington,A;James,WD;Peacocke,M
肿瘤细胞代表了在基因组DNA中经历了一系列突变的细胞的单一克隆。这一过程被称为克隆进化，是癌症的一个显著特征。人类雄激素受体基因（HUMARA; GenBank）包含一个高度多态性的胞嘧啶-腺嘌呤-鸟嘌呤三核苷酸重复序列，可以通过描述X染色体失活模式来确定克隆性。随机X染色体失活与多克隆一致；非随机X染色体失活表明细胞的克隆群体。基底细胞癌（BCC）表现出一种非典型的生长模式，因为它生长缓慢，很少转移，很少致命。这种肿瘤是由单细胞突变积累引起的，随后是克隆扩增，还是反映了一群细胞对生长刺激的多克隆反应，目前尚不清楚。为了进一步了解bcc的分子事件特征，我们通过分析HUMARA位点的X染色体失活模式，确定了来自一位女性患者的5例结节性bcc的克隆起源。所有肿瘤均表现出X染色体失活的非随机模式，与单克隆增殖一致。这些发现提供了强有力的遗传证据，证明散发性bcc是通过克隆进化形成的，并支持了单细胞中的一系列突变是这些转化上皮细胞生长状态改变的原因。
Tumor cells represent a single clone of cells that have undergone a series of mutations in genomic DNA. This process, known as clonal evolution, is a distinguishing feature of cancer. The human androgen receptor gene (HUMARA; GenBank) contains a highly polymorphic cytosine-adenine-guanine trinucleotide repeat that can be used to determine clonality by depicting X chromosome inactivation patterns. Random X chromosome inactivation is consistent with polyclonality; nonrandom X chromosome inactivation indicates a clonal population of cells. Basal cell carcinoma (BCC) demonstrates an atypical growth pattern in that it grows slowly, rarely metastasizes, and is rarely lethal. Whether this tumor results from the accumulation of mutations in a single cell with subsequent clonal expansion or reflects a polyclonal response by a group of cells to a growth stimulus is unknown. To provide further insight into the molecular events characterizing BCCs, we determined the clonal origin of five nodular BCCs from a female patient by analyzing X chromosome inactivation patterns at the HUMARA locus. All tumors demonstrated a nonrandom pattern of X chromosome inactivation, consistent with monoclonal proliferation. These findings provide strong genetic evidence that sporadic BCCs develop by clonal evolution and support the contention that a series of mutations in a single cell is responsible for the altered growth state seen in these transformed epithelial cells.