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APOBEC3B 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...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6721358/
https://www.ncbi.nlm.nih.gov/pubmed/31357602
http://dx.doi.org/10.3390/cancers11081062
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author 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.
author_facet 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.
author_sort Sieuwerts, Anieta M.
collection PubMed
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 APOBEC3B 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. APOBEC3B 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 APOBEC3B. No differences in expression were found between DCIS and IBC. Subgroup analysis showed that APOBEC3B was the highest in the ER subgroups of DCIS and IBC. While there was no difference in APOBEC3B between wild-type versus mutated PIK3CA DCIS, APOBEC3B was higher in wild-type versus PIK3CA-mutated IBC. In summary, our data show that APOBEC3B 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.
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spelling pubmed-67213582019-09-10 APOBEC3B Gene Expression in Ductal Carcinoma In Situ and Synchronous Invasive Breast Cancer 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. Cancers (Basel) Article 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 APOBEC3B 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. APOBEC3B 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 APOBEC3B. No differences in expression were found between DCIS and IBC. Subgroup analysis showed that APOBEC3B was the highest in the ER subgroups of DCIS and IBC. While there was no difference in APOBEC3B between wild-type versus mutated PIK3CA DCIS, APOBEC3B was higher in wild-type versus PIK3CA-mutated IBC. In summary, our data show that APOBEC3B 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. MDPI 2019-07-27 /pmc/articles/PMC6721358/ /pubmed/31357602 http://dx.doi.org/10.3390/cancers11081062 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
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.
APOBEC3B Gene Expression in Ductal Carcinoma In Situ and Synchronous Invasive Breast Cancer
title APOBEC3B Gene Expression in Ductal Carcinoma In Situ and Synchronous Invasive Breast Cancer
title_full APOBEC3B Gene Expression in Ductal Carcinoma In Situ and Synchronous Invasive Breast Cancer
title_fullStr APOBEC3B Gene Expression in Ductal Carcinoma In Situ and Synchronous Invasive Breast Cancer
title_full_unstemmed APOBEC3B Gene Expression in Ductal Carcinoma In Situ and Synchronous Invasive Breast Cancer
title_short APOBEC3B Gene Expression in Ductal Carcinoma In Situ and Synchronous Invasive Breast Cancer
title_sort apobec3b gene expression in ductal carcinoma in situ and synchronous invasive breast cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6721358/
https://www.ncbi.nlm.nih.gov/pubmed/31357602
http://dx.doi.org/10.3390/cancers11081062
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