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Whole Transcriptome RNA-Seq Analysis of Breast Cancer Recurrence Risk Using Formalin-Fixed Paraffin-Embedded Tumor Tissue
RNA biomarkers discovered by RT-PCR-based gene expression profiling of archival formalin-fixed paraffin-embedded (FFPE) tissue form the basis for widely used clinical diagnostic tests; however, RT-PCR is practically constrained in the number of transcripts that can be interrogated. We have developed...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3396611/ https://www.ncbi.nlm.nih.gov/pubmed/22808097 http://dx.doi.org/10.1371/journal.pone.0040092 |
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author | Sinicropi, Dominick Qu, Kunbin Collin, Francois Crager, Michael Liu, Mei-Lan Pelham, Robert J. Pho, Mylan Rossi, Andrew Dei Jeong, Jennie Scott, Aaron Ambannavar, Ranjana Zheng, Christina Mena, Raul Esteban, Jose Stephans, James Morlan, John Baker, Joffre |
author_facet | Sinicropi, Dominick Qu, Kunbin Collin, Francois Crager, Michael Liu, Mei-Lan Pelham, Robert J. Pho, Mylan Rossi, Andrew Dei Jeong, Jennie Scott, Aaron Ambannavar, Ranjana Zheng, Christina Mena, Raul Esteban, Jose Stephans, James Morlan, John Baker, Joffre |
author_sort | Sinicropi, Dominick |
collection | PubMed |
description | RNA biomarkers discovered by RT-PCR-based gene expression profiling of archival formalin-fixed paraffin-embedded (FFPE) tissue form the basis for widely used clinical diagnostic tests; however, RT-PCR is practically constrained in the number of transcripts that can be interrogated. We have developed and optimized RNA-Seq library chemistry as well as bioinformatics and biostatistical methods for whole transcriptome profiling from FFPE tissue. The chemistry accommodates low RNA inputs and sample multiplexing. These methods both enable rediscovery of RNA biomarkers for disease recurrence risk that were previously identified by RT-PCR analysis of a cohort of 136 patients, and also identify a high percentage of recurrence risk markers that were previously discovered using DNA microarrays in a separate cohort of patients, evidence that this RNA-Seq technology has sufficient precision and sensitivity for biomarker discovery. More than two thousand RNAs are strongly associated with breast cancer recurrence risk in the 136 patient cohort (FDR <10%). Many of these are intronic RNAs for which corresponding exons are not also associated with disease recurrence. A number of the RNAs associated with recurrence risk belong to novel RNA networks. It will be important to test the validity of these novel associations in whole transcriptome RNA-Seq screens of other breast cancer cohorts. |
format | Online Article Text |
id | pubmed-3396611 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-33966112012-07-17 Whole Transcriptome RNA-Seq Analysis of Breast Cancer Recurrence Risk Using Formalin-Fixed Paraffin-Embedded Tumor Tissue Sinicropi, Dominick Qu, Kunbin Collin, Francois Crager, Michael Liu, Mei-Lan Pelham, Robert J. Pho, Mylan Rossi, Andrew Dei Jeong, Jennie Scott, Aaron Ambannavar, Ranjana Zheng, Christina Mena, Raul Esteban, Jose Stephans, James Morlan, John Baker, Joffre PLoS One Research Article RNA biomarkers discovered by RT-PCR-based gene expression profiling of archival formalin-fixed paraffin-embedded (FFPE) tissue form the basis for widely used clinical diagnostic tests; however, RT-PCR is practically constrained in the number of transcripts that can be interrogated. We have developed and optimized RNA-Seq library chemistry as well as bioinformatics and biostatistical methods for whole transcriptome profiling from FFPE tissue. The chemistry accommodates low RNA inputs and sample multiplexing. These methods both enable rediscovery of RNA biomarkers for disease recurrence risk that were previously identified by RT-PCR analysis of a cohort of 136 patients, and also identify a high percentage of recurrence risk markers that were previously discovered using DNA microarrays in a separate cohort of patients, evidence that this RNA-Seq technology has sufficient precision and sensitivity for biomarker discovery. More than two thousand RNAs are strongly associated with breast cancer recurrence risk in the 136 patient cohort (FDR <10%). Many of these are intronic RNAs for which corresponding exons are not also associated with disease recurrence. A number of the RNAs associated with recurrence risk belong to novel RNA networks. It will be important to test the validity of these novel associations in whole transcriptome RNA-Seq screens of other breast cancer cohorts. Public Library of Science 2012-07-13 /pmc/articles/PMC3396611/ /pubmed/22808097 http://dx.doi.org/10.1371/journal.pone.0040092 Text en Sinicropi 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, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Sinicropi, Dominick Qu, Kunbin Collin, Francois Crager, Michael Liu, Mei-Lan Pelham, Robert J. Pho, Mylan Rossi, Andrew Dei Jeong, Jennie Scott, Aaron Ambannavar, Ranjana Zheng, Christina Mena, Raul Esteban, Jose Stephans, James Morlan, John Baker, Joffre Whole Transcriptome RNA-Seq Analysis of Breast Cancer Recurrence Risk Using Formalin-Fixed Paraffin-Embedded Tumor Tissue |
title | Whole Transcriptome RNA-Seq Analysis of Breast Cancer Recurrence Risk Using Formalin-Fixed Paraffin-Embedded Tumor Tissue |
title_full | Whole Transcriptome RNA-Seq Analysis of Breast Cancer Recurrence Risk Using Formalin-Fixed Paraffin-Embedded Tumor Tissue |
title_fullStr | Whole Transcriptome RNA-Seq Analysis of Breast Cancer Recurrence Risk Using Formalin-Fixed Paraffin-Embedded Tumor Tissue |
title_full_unstemmed | Whole Transcriptome RNA-Seq Analysis of Breast Cancer Recurrence Risk Using Formalin-Fixed Paraffin-Embedded Tumor Tissue |
title_short | Whole Transcriptome RNA-Seq Analysis of Breast Cancer Recurrence Risk Using Formalin-Fixed Paraffin-Embedded Tumor Tissue |
title_sort | whole transcriptome rna-seq analysis of breast cancer recurrence risk using formalin-fixed paraffin-embedded tumor tissue |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3396611/ https://www.ncbi.nlm.nih.gov/pubmed/22808097 http://dx.doi.org/10.1371/journal.pone.0040092 |
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