Sieuwerts Anieta M, Doebar Shusma C, de Weerd Vanja, Verhoef Esther I, Beauford Corine M, Agahozo Marie C, Martens John W M, van Deurzen Carolien H M
Department of Medical Oncology and Erasmus MC Cancer Institute, 3015 GD Rotterdam, The Netherlands.
Cancer Genomics Netherlands, Erasmus MC Cancer Institute, 3015 GD Rotterdam, The Netherlands.
Cancers (Basel). 2019 Jul 27;11(8):1062. doi: 10.3390/cancers11081062.
The underlying mechanism of the progression of ductal carcinoma in situ (DCIS), a non-obligate precursor of invasive breast cancer (IBC), has yet to be elucidated. In IBC, Apolipoprotein B mRNA Editing Enzyme, Catalytic Polypeptide-Like 3B (APOBEC3B) is upregulated in a substantial proportion of cases and is associated with higher mutational load and poor prognosis. However, APOBEC3B expression has never been studied in DCIS. We performed mRNA expression analysis of in synchronous DCIS and IBC and surrounding normal cells. RNA was obtained from 53 patients. The tumors were categorized based on estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (Her2) and phosphoinositide-3-kinase, catalytic, alpha polypeptide (PIK3CA) mutation status. mRNA levels were measured by RT-qPCR. The expression levels of paired DCIS and adjacent IBC were compared, including subgroup analyses. The normal cells expressed the lowest levels of . No differences in expression were found between DCIS and IBC. Subgroup analysis showed that was the highest in the ER subgroups of DCIS and IBC. While there was no difference in between wild-type versus mutated PIK3CA DCIS, was higher in wild-type versus PIK3CA-mutated IBC. In summary, our data show that is already upregulated in DCIS. This suggests that APOBEC3B could already play a role in early carcinogenesis. Since APOBEC3B is a gain-of-function mutagenic enzyme, patients could benefit from the therapeutic targeting of APOBEC3B in the early non-invasive stage of breast cancer.
导管原位癌（DCIS）是浸润性乳腺癌（IBC）的一种非必然前体，其进展的潜在机制尚未阐明。在IBC中，载脂蛋白B mRNA编辑酶催化多肽样3B（APOBEC3B）在相当一部分病例中上调，并且与更高的突变负荷和不良预后相关。然而，APOBEC3B在DCIS中的表达从未被研究过。我们对同步发生的DCIS、IBC及周围正常细胞进行了mRNA表达分析。从53例患者中获取了RNA。根据雌激素受体（ER）、孕激素受体（PR）、人表皮生长因子受体2（Her2）和磷酸肌醇-3-激酶催化亚基α多肽（PIK3CA）的突变状态对肿瘤进行分类。通过RT-qPCR测量mRNA水平。比较了配对的DCIS和相邻IBC的表达水平，包括亚组分析。正常细胞表达的[具体基因名称]水平最低。DCIS和IBC之间未发现表达差异。亚组分析表明，[具体基因名称]在DCIS和IBC的ER亚组中最高。虽然野生型与PIK3CA突变型DCIS之间的[具体基因名称]无差异，但野生型IBC与PIK3CA突变型IBC相比，[具体基因名称]更高。总之，我们的数据表明[具体基因名称]在DCIS中已经上调。这表明APOBEC3B可能已经在早期致癌过程中发挥作用。由于APOBEC3B是一种功能获得性诱变酶，患者可能会从乳腺癌早期非侵袭阶段针对APOBEC3B的治疗靶向中获益。
