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Progressive APOBEC3B mRNA expression in distant breast cancer metastases

BACKGROUND: APOBEC3B was recently identified as a gain-of-function enzymatic source of mutagenesis, which may offer novel therapeutic options with molecules that specifically target this enzyme. In primary breast cancer, APOBEC3B mRNA is deregulated in a substantial proportion of cases and its expre...

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Autores principales: Sieuwerts, Anieta M., Schrijver, Willemijne A. M. E., Dalm, Simone U., de Weerd, Vanja, Moelans, Cathy B., ter Hoeve, Natalie, van Diest, Paul J., Martens, John W. M., van Deurzen, Carolien H. M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5283735/
https://www.ncbi.nlm.nih.gov/pubmed/28141868
http://dx.doi.org/10.1371/journal.pone.0171343
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author Sieuwerts, Anieta M.
Schrijver, Willemijne A. M. E.
Dalm, Simone U.
de Weerd, Vanja
Moelans, Cathy B.
ter Hoeve, Natalie
van Diest, Paul J.
Martens, John W. M.
van Deurzen, Carolien H. M.
author_facet Sieuwerts, Anieta M.
Schrijver, Willemijne A. M. E.
Dalm, Simone U.
de Weerd, Vanja
Moelans, Cathy B.
ter Hoeve, Natalie
van Diest, Paul J.
Martens, John W. M.
van Deurzen, Carolien H. M.
author_sort Sieuwerts, Anieta M.
collection PubMed
description BACKGROUND: APOBEC3B was recently identified as a gain-of-function enzymatic source of mutagenesis, which may offer novel therapeutic options with molecules that specifically target this enzyme. In primary breast cancer, APOBEC3B mRNA is deregulated in a substantial proportion of cases and its expression is associated with poor prognosis. However, its expression in breast cancer metastases, which are the main causes of breast cancer-related death, remained to be elucidated. PATIENTS AND METHODS: RNA was isolated from 55 primary breast cancers and paired metastases, including regional lymph node (N = 20) and distant metastases (N = 35). APOBEC3B mRNA levels were measured by RT-qPCR. Expression levels of the primary tumors and corresponding metastases were compared, including subgroup analysis by estrogen receptor (ER/ESR1) status. RESULTS: Overall, APOBEC3B mRNA levels of distant metastases were significantly higher as compared to the corresponding primary breast tumor (P = 0.0015), an effect that was not seen for loco-regional lymph node metastases (P = 0.23). Subgroup analysis by ER-status showed that increased APOBEC3B levels in distant metastases were restricted to metastases arising from ER-positive primary breast cancers (P = 0.002). However, regarding ER-negative primary tumors, only loco-regional lymph node metastases showed increased APOBEC3B expression when compared to the corresponding primary tumor (P = 0.028). CONCLUSION: APOBEC3B mRNA levels are significantly higher in breast cancer metastases as compared to the corresponding ER-positive primary tumors. This suggests a potential role for APOBEC3B in luminal breast cancer progression, and consequently, a promising role for anti-APOBEC3B therapies in advanced stages of this frequent form of breast cancer.
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spelling pubmed-52837352017-02-17 Progressive APOBEC3B mRNA expression in distant breast cancer metastases Sieuwerts, Anieta M. Schrijver, Willemijne A. M. E. Dalm, Simone U. de Weerd, Vanja Moelans, Cathy B. ter Hoeve, Natalie van Diest, Paul J. Martens, John W. M. van Deurzen, Carolien H. M. PLoS One Research Article BACKGROUND: APOBEC3B was recently identified as a gain-of-function enzymatic source of mutagenesis, which may offer novel therapeutic options with molecules that specifically target this enzyme. In primary breast cancer, APOBEC3B mRNA is deregulated in a substantial proportion of cases and its expression is associated with poor prognosis. However, its expression in breast cancer metastases, which are the main causes of breast cancer-related death, remained to be elucidated. PATIENTS AND METHODS: RNA was isolated from 55 primary breast cancers and paired metastases, including regional lymph node (N = 20) and distant metastases (N = 35). APOBEC3B mRNA levels were measured by RT-qPCR. Expression levels of the primary tumors and corresponding metastases were compared, including subgroup analysis by estrogen receptor (ER/ESR1) status. RESULTS: Overall, APOBEC3B mRNA levels of distant metastases were significantly higher as compared to the corresponding primary breast tumor (P = 0.0015), an effect that was not seen for loco-regional lymph node metastases (P = 0.23). Subgroup analysis by ER-status showed that increased APOBEC3B levels in distant metastases were restricted to metastases arising from ER-positive primary breast cancers (P = 0.002). However, regarding ER-negative primary tumors, only loco-regional lymph node metastases showed increased APOBEC3B expression when compared to the corresponding primary tumor (P = 0.028). CONCLUSION: APOBEC3B mRNA levels are significantly higher in breast cancer metastases as compared to the corresponding ER-positive primary tumors. This suggests a potential role for APOBEC3B in luminal breast cancer progression, and consequently, a promising role for anti-APOBEC3B therapies in advanced stages of this frequent form of breast cancer. Public Library of Science 2017-01-31 /pmc/articles/PMC5283735/ /pubmed/28141868 http://dx.doi.org/10.1371/journal.pone.0171343 Text en © 2017 Sieuwerts et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Sieuwerts, Anieta M.
Schrijver, Willemijne A. M. E.
Dalm, Simone U.
de Weerd, Vanja
Moelans, Cathy B.
ter Hoeve, Natalie
van Diest, Paul J.
Martens, John W. M.
van Deurzen, Carolien H. M.
Progressive APOBEC3B mRNA expression in distant breast cancer metastases
title Progressive APOBEC3B mRNA expression in distant breast cancer metastases
title_full Progressive APOBEC3B mRNA expression in distant breast cancer metastases
title_fullStr Progressive APOBEC3B mRNA expression in distant breast cancer metastases
title_full_unstemmed Progressive APOBEC3B mRNA expression in distant breast cancer metastases
title_short Progressive APOBEC3B mRNA expression in distant breast cancer metastases
title_sort progressive apobec3b mrna expression in distant breast cancer metastases
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5283735/
https://www.ncbi.nlm.nih.gov/pubmed/28141868
http://dx.doi.org/10.1371/journal.pone.0171343
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