Department of Surgical Sciences, Uppsala University, Uppsala SE 75105, Sweden.
Mol Oncol. 2009 Jun;3(3):214-9. doi: 10.1016/j.molonc.2009.03.001. Epub 2009 Apr 2.
In breast cancer, previous studies have suggested that somatic TP53 mutations are likely to be an early event. However, there are controversies regarding the cellular origin and linear course of breast cancer. The purpose of this study was to investigate tumor evolution in breast cancer by analyzing TP53 mutation status in tumors from various stages of the disease. The entire coding sequence of TP53 was sequenced in a cohort of pure ductal carcinoma in situ (DCIS), pure invasive cancer (≤15mm) and mixed lesions (i.e. invasive cancer with an in situ component). Of 118 tumor samples, 19 were found to harbor a TP53 mutation; 5 (15.6%) of the pure DCIS, 4 (10.5%) of the pure invasive cancers and 10 (20.8%) of the mixed lesions. In the mixed lesions, both the invasive and the DCIS components showed the same mutation in all 5 cases where the two components were successfully microdissected. Presence of the same mutation in both DCIS and invasive components from the same tumor indicates same cellular origin. The role of mutant TP53 in the progression of breast cancer is less clear and may vary between subtypes.
在乳腺癌中，先前的研究表明，体细胞 TP53 突变可能是早期事件。然而，关于乳腺癌的细胞起源和线性病程仍存在争议。本研究旨在通过分析不同疾病阶段肿瘤的 TP53 突变状态来研究乳腺癌的肿瘤演变。我们对纯导管原位癌（DCIS）、纯浸润性癌（≤15mm）和混合病变（即浸润性癌伴原位成分）的肿瘤进行了 TP53 全长编码序列测序。在 118 个肿瘤样本中，发现 19 个样本携带有 TP53 突变；纯 DCIS 中有 5 个（15.6%），纯浸润性癌中有 4 个（10.5%），混合病变中有 10 个（20.8%）。在 5 例成功微切割的混合病变中，侵袭性成分和 DCIS 成分均显示出相同的突变。同一肿瘤的 DCIS 和浸润性成分存在相同的突变表明具有相同的细胞起源。突变型 TP53 在乳腺癌进展中的作用尚不清楚，并且可能在不同亚型之间存在差异。
