<i>APOBEC3B</i> Gene Expression in Ductal Carcinoma In Situ and Synchronous Invasive Breast Cancer
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 cas...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2019-07-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/11/8/1062 |
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| author | Anieta M. Sieuwerts Shusma C. Doebar Vanja de Weerd Esther I. Verhoef Corine M. Beauford Marie C. Agahozo John W.M. Martens Carolien H.M. van Deurzen |
| author_facet | Anieta M. Sieuwerts Shusma C. Doebar Vanja de Weerd Esther I. Verhoef Corine M. Beauford Marie C. Agahozo John W.M. Martens Carolien H.M. van Deurzen |
| author_sort | Anieta M. Sieuwerts |
| collection | DOAJ |
| description | 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 <i>APOBEC3B</i> 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. <i>APOBEC3B</i> 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 <i>APOBEC3B</i>. No differences in expression were found between DCIS and IBC. Subgroup analysis showed that <i>APOBEC3B</i> was the highest in the ER subgroups of DCIS and IBC. While there was no difference in <i>APOBEC3B</i> between wild-type versus mutated PIK3CA DCIS, <i>APOBEC3B</i> was higher in wild-type versus PIK3CA-mutated IBC. In summary, our data show that <i>APOBEC3B</i> 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. |
| first_indexed | 2024-03-12T04:41:37Z |
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| id | doaj.art-14518df8bad24cc4989e6ccc4180c2d5 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-12T04:41:37Z |
| publishDate | 2019-07-01 |
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| series | Cancers |
| spelling | doaj.art-14518df8bad24cc4989e6ccc4180c2d52023-09-03T09:33:46ZengMDPI AGCancers2072-66942019-07-01118106210.3390/cancers11081062cancers11081062<i>APOBEC3B</i> Gene Expression in Ductal Carcinoma In Situ and Synchronous Invasive Breast CancerAnieta M. Sieuwerts0Shusma C. Doebar1Vanja de Weerd2Esther I. Verhoef3Corine M. Beauford4Marie C. Agahozo5John W.M. Martens6Carolien H.M. van Deurzen7Department of Medical Oncology and Erasmus MC Cancer Institute, 3015 GD Rotterdam, The NetherlandsDepartment of Pathology, Erasmus MC Cancer Institute, 3015 GD Rotterdam, The NetherlandsDepartment of Medical Oncology and Erasmus MC Cancer Institute, 3015 GD Rotterdam, The NetherlandsDepartment of Pathology, Erasmus MC Cancer Institute, 3015 GD Rotterdam, The NetherlandsDepartment of Medical Oncology and Erasmus MC Cancer Institute, 3015 GD Rotterdam, The NetherlandsDepartment of Pathology, Erasmus MC Cancer Institute, 3015 GD Rotterdam, The NetherlandsDepartment of Medical Oncology and Erasmus MC Cancer Institute, 3015 GD Rotterdam, The NetherlandsDepartment of Pathology, Erasmus MC Cancer Institute, 3015 GD Rotterdam, The NetherlandsThe 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 <i>APOBEC3B</i> 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. <i>APOBEC3B</i> 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 <i>APOBEC3B</i>. No differences in expression were found between DCIS and IBC. Subgroup analysis showed that <i>APOBEC3B</i> was the highest in the ER subgroups of DCIS and IBC. While there was no difference in <i>APOBEC3B</i> between wild-type versus mutated PIK3CA DCIS, <i>APOBEC3B</i> was higher in wild-type versus PIK3CA-mutated IBC. In summary, our data show that <i>APOBEC3B</i> 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.https://www.mdpi.com/2072-6694/11/8/1062APOBEC3Bgene expressionbreast cancerductal carcinoma in situinfiltrating breast cancerPIK3CA |
| spellingShingle | Anieta M. Sieuwerts Shusma C. Doebar Vanja de Weerd Esther I. Verhoef Corine M. Beauford Marie C. Agahozo John W.M. Martens Carolien H.M. van Deurzen <i>APOBEC3B</i> Gene Expression in Ductal Carcinoma In Situ and Synchronous Invasive Breast Cancer Cancers APOBEC3B gene expression breast cancer ductal carcinoma in situ infiltrating breast cancer PIK3CA |
| title | <i>APOBEC3B</i> Gene Expression in Ductal Carcinoma In Situ and Synchronous Invasive Breast Cancer |
| title_full | <i>APOBEC3B</i> Gene Expression in Ductal Carcinoma In Situ and Synchronous Invasive Breast Cancer |
| title_fullStr | <i>APOBEC3B</i> Gene Expression in Ductal Carcinoma In Situ and Synchronous Invasive Breast Cancer |
| title_full_unstemmed | <i>APOBEC3B</i> Gene Expression in Ductal Carcinoma In Situ and Synchronous Invasive Breast Cancer |
| title_short | <i>APOBEC3B</i> Gene Expression in Ductal Carcinoma In Situ and Synchronous Invasive Breast Cancer |
| title_sort | i apobec3b i gene expression in ductal carcinoma in situ and synchronous invasive breast cancer |
| topic | APOBEC3B gene expression breast cancer ductal carcinoma in situ infiltrating breast cancer PIK3CA |
| url | https://www.mdpi.com/2072-6694/11/8/1062 |
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