Cargando…
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...
Autores principales: | , , , , , , , |
---|---|
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 |
_version_ | 1783448326475087872 |
---|---|
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. |
format | Online Article Text |
id | pubmed-6721358 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT sieuwertsanietam apobec3bgeneexpressioninductalcarcinomainsituandsynchronousinvasivebreastcancer AT doebarshusmac apobec3bgeneexpressioninductalcarcinomainsituandsynchronousinvasivebreastcancer AT deweerdvanja apobec3bgeneexpressioninductalcarcinomainsituandsynchronousinvasivebreastcancer AT verhoefestheri apobec3bgeneexpressioninductalcarcinomainsituandsynchronousinvasivebreastcancer AT beaufordcorinem apobec3bgeneexpressioninductalcarcinomainsituandsynchronousinvasivebreastcancer AT agahozomariec apobec3bgeneexpressioninductalcarcinomainsituandsynchronousinvasivebreastcancer AT martensjohnwm apobec3bgeneexpressioninductalcarcinomainsituandsynchronousinvasivebreastcancer AT vandeurzencarolienhm apobec3bgeneexpressioninductalcarcinomainsituandsynchronousinvasivebreastcancer |