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APOBEC3A is a prominent cytidine deaminase in breast cancer
APOBEC cytidine deaminases are the second-most prominent source of mutagenesis in sequenced tumors. Previous studies have proposed that APOBEC3B (A3B) is the major source of mutagenesis in breast cancer (BRCA). We show that APOBEC3A (A3A) is the only APOBEC whose expression correlates with APOBEC-in...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6936861/ https://www.ncbi.nlm.nih.gov/pubmed/31841499 http://dx.doi.org/10.1371/journal.pgen.1008545 |
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author | Cortez, Luis M. Brown, Amber L. Dennis, Madeline A. Collins, Christopher D. Brown, Alexander J. Mitchell, Debra Mertz, Tony M. Roberts, Steven A. |
author_facet | Cortez, Luis M. Brown, Amber L. Dennis, Madeline A. Collins, Christopher D. Brown, Alexander J. Mitchell, Debra Mertz, Tony M. Roberts, Steven A. |
author_sort | Cortez, Luis M. |
collection | PubMed |
description | APOBEC cytidine deaminases are the second-most prominent source of mutagenesis in sequenced tumors. Previous studies have proposed that APOBEC3B (A3B) is the major source of mutagenesis in breast cancer (BRCA). We show that APOBEC3A (A3A) is the only APOBEC whose expression correlates with APOBEC-induced mutation load and that A3A expression is responsible for cytidine deamination in multiple BRCA cell lines. Comparative analysis of A3A and A3B expression by qRT-PCR, RSEM-normalized RNA-seq, and unambiguous RNA-seq validated the use of RNA-seq to measure APOBEC expression, which indicates that A3A is the primary correlate with APOBEC-mutation load in primary BRCA tumors. We also demonstrate that A3A has >100-fold more cytidine deamination activity than A3B in the presence of cellular RNA, likely explaining why higher levels of A3B expression contributes less to mutagenesis in BRCA. Our findings identify A3A as a major source of cytidine deaminase activity in breast cancer cells and possibly a prominent contributor to the APOBEC mutation signature. |
format | Online Article Text |
id | pubmed-6936861 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-69368612020-01-07 APOBEC3A is a prominent cytidine deaminase in breast cancer Cortez, Luis M. Brown, Amber L. Dennis, Madeline A. Collins, Christopher D. Brown, Alexander J. Mitchell, Debra Mertz, Tony M. Roberts, Steven A. PLoS Genet Research Article APOBEC cytidine deaminases are the second-most prominent source of mutagenesis in sequenced tumors. Previous studies have proposed that APOBEC3B (A3B) is the major source of mutagenesis in breast cancer (BRCA). We show that APOBEC3A (A3A) is the only APOBEC whose expression correlates with APOBEC-induced mutation load and that A3A expression is responsible for cytidine deamination in multiple BRCA cell lines. Comparative analysis of A3A and A3B expression by qRT-PCR, RSEM-normalized RNA-seq, and unambiguous RNA-seq validated the use of RNA-seq to measure APOBEC expression, which indicates that A3A is the primary correlate with APOBEC-mutation load in primary BRCA tumors. We also demonstrate that A3A has >100-fold more cytidine deamination activity than A3B in the presence of cellular RNA, likely explaining why higher levels of A3B expression contributes less to mutagenesis in BRCA. Our findings identify A3A as a major source of cytidine deaminase activity in breast cancer cells and possibly a prominent contributor to the APOBEC mutation signature. Public Library of Science 2019-12-16 /pmc/articles/PMC6936861/ /pubmed/31841499 http://dx.doi.org/10.1371/journal.pgen.1008545 Text en © 2019 Cortez 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 Cortez, Luis M. Brown, Amber L. Dennis, Madeline A. Collins, Christopher D. Brown, Alexander J. Mitchell, Debra Mertz, Tony M. Roberts, Steven A. APOBEC3A is a prominent cytidine deaminase in breast cancer |
title | APOBEC3A is a prominent cytidine deaminase in breast cancer |
title_full | APOBEC3A is a prominent cytidine deaminase in breast cancer |
title_fullStr | APOBEC3A is a prominent cytidine deaminase in breast cancer |
title_full_unstemmed | APOBEC3A is a prominent cytidine deaminase in breast cancer |
title_short | APOBEC3A is a prominent cytidine deaminase in breast cancer |
title_sort | apobec3a is a prominent cytidine deaminase in breast cancer |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6936861/ https://www.ncbi.nlm.nih.gov/pubmed/31841499 http://dx.doi.org/10.1371/journal.pgen.1008545 |
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