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Personalized oncogenomic analysis of metastatic adenoid cystic carcinoma: using whole-genome sequencing to inform clinical decision-making
Metastatic adenoid cystic carcinomas (ACCs) can cause significant morbidity and mortality. Because of their slow growth and relative rarity, there is limited evidence for systemic therapy regimens. Recently, molecular profiling studies have begun to reveal the genetic landscape of these poorly under...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory Press
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5880267/ https://www.ncbi.nlm.nih.gov/pubmed/29610392 http://dx.doi.org/10.1101/mcs.a002626 |
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author | Chahal, Manik Pleasance, Erin Grewal, Jasleen Zhao, Eric Ng, Tony Chapman, Erin Jones, Martin R. Shen, Yaoqing Mungall, Karen L. Bonakdar, Melika Taylor, Gregory A. Ma, Yussanne Mungall, Andrew J. Moore, Richard A. Lim, Howard Renouf, Daniel Yip, Stephen Jones, Steven J.M. Marra, Marco A. Laskin, Janessa |
author_facet | Chahal, Manik Pleasance, Erin Grewal, Jasleen Zhao, Eric Ng, Tony Chapman, Erin Jones, Martin R. Shen, Yaoqing Mungall, Karen L. Bonakdar, Melika Taylor, Gregory A. Ma, Yussanne Mungall, Andrew J. Moore, Richard A. Lim, Howard Renouf, Daniel Yip, Stephen Jones, Steven J.M. Marra, Marco A. Laskin, Janessa |
author_sort | Chahal, Manik |
collection | PubMed |
description | Metastatic adenoid cystic carcinomas (ACCs) can cause significant morbidity and mortality. Because of their slow growth and relative rarity, there is limited evidence for systemic therapy regimens. Recently, molecular profiling studies have begun to reveal the genetic landscape of these poorly understood cancers, and new treatment possibilities are beginning to emerge. The objective is to use whole-genome and transcriptome sequencing and analysis to better understand the genetic alterations underlying the pathology of metastatic and rare ACCs and determine potentially actionable therapeutic targets. We report five cases of metastatic ACC, not originating in the salivary glands, in patients enrolled in the Personalized Oncogenomics (POG) Program at the BC Cancer Agency. Genomic workup included whole-genome and transcriptome sequencing, detailed analysis of tumor alterations, and integration with existing knowledge of drug–target combinations to identify potential therapeutic targets. Analysis reveals low mutational burden in these five ACC cases, and mutation signatures that are commonly observed in multiple cancer types. Notably, the only recurrent structural aberration identified was the well-described MYB-NFIB fusion that was present in four of five cases, and one case exhibited a closely related MYBL1-NFIB fusion. Recurrent mutations were also identified in BAP1 and BCOR, with additional mutations in individual samples affecting NOTCH1 and the epigenetic regulators ARID2, SMARCA2, and SMARCB1. Copy changes were rare, and they included amplification of MYC and homozygous loss of CDKN2A in individual samples. Genomic analysis revealed therapeutic targets in all five cases and served to inform a therapeutic choice in three of the cases to date. |
format | Online Article Text |
id | pubmed-5880267 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Cold Spring Harbor Laboratory Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-58802672018-04-13 Personalized oncogenomic analysis of metastatic adenoid cystic carcinoma: using whole-genome sequencing to inform clinical decision-making Chahal, Manik Pleasance, Erin Grewal, Jasleen Zhao, Eric Ng, Tony Chapman, Erin Jones, Martin R. Shen, Yaoqing Mungall, Karen L. Bonakdar, Melika Taylor, Gregory A. Ma, Yussanne Mungall, Andrew J. Moore, Richard A. Lim, Howard Renouf, Daniel Yip, Stephen Jones, Steven J.M. Marra, Marco A. Laskin, Janessa Cold Spring Harb Mol Case Stud Research Article Metastatic adenoid cystic carcinomas (ACCs) can cause significant morbidity and mortality. Because of their slow growth and relative rarity, there is limited evidence for systemic therapy regimens. Recently, molecular profiling studies have begun to reveal the genetic landscape of these poorly understood cancers, and new treatment possibilities are beginning to emerge. The objective is to use whole-genome and transcriptome sequencing and analysis to better understand the genetic alterations underlying the pathology of metastatic and rare ACCs and determine potentially actionable therapeutic targets. We report five cases of metastatic ACC, not originating in the salivary glands, in patients enrolled in the Personalized Oncogenomics (POG) Program at the BC Cancer Agency. Genomic workup included whole-genome and transcriptome sequencing, detailed analysis of tumor alterations, and integration with existing knowledge of drug–target combinations to identify potential therapeutic targets. Analysis reveals low mutational burden in these five ACC cases, and mutation signatures that are commonly observed in multiple cancer types. Notably, the only recurrent structural aberration identified was the well-described MYB-NFIB fusion that was present in four of five cases, and one case exhibited a closely related MYBL1-NFIB fusion. Recurrent mutations were also identified in BAP1 and BCOR, with additional mutations in individual samples affecting NOTCH1 and the epigenetic regulators ARID2, SMARCA2, and SMARCB1. Copy changes were rare, and they included amplification of MYC and homozygous loss of CDKN2A in individual samples. Genomic analysis revealed therapeutic targets in all five cases and served to inform a therapeutic choice in three of the cases to date. Cold Spring Harbor Laboratory Press 2018-04 /pmc/articles/PMC5880267/ /pubmed/29610392 http://dx.doi.org/10.1101/mcs.a002626 Text en © 2018 Chahal et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/) , which permits reuse and redistribution, except for commercial purposes, provided that the original author and source are credited. |
spellingShingle | Research Article Chahal, Manik Pleasance, Erin Grewal, Jasleen Zhao, Eric Ng, Tony Chapman, Erin Jones, Martin R. Shen, Yaoqing Mungall, Karen L. Bonakdar, Melika Taylor, Gregory A. Ma, Yussanne Mungall, Andrew J. Moore, Richard A. Lim, Howard Renouf, Daniel Yip, Stephen Jones, Steven J.M. Marra, Marco A. Laskin, Janessa Personalized oncogenomic analysis of metastatic adenoid cystic carcinoma: using whole-genome sequencing to inform clinical decision-making |
title | Personalized oncogenomic analysis of metastatic adenoid cystic carcinoma: using whole-genome sequencing to inform clinical decision-making |
title_full | Personalized oncogenomic analysis of metastatic adenoid cystic carcinoma: using whole-genome sequencing to inform clinical decision-making |
title_fullStr | Personalized oncogenomic analysis of metastatic adenoid cystic carcinoma: using whole-genome sequencing to inform clinical decision-making |
title_full_unstemmed | Personalized oncogenomic analysis of metastatic adenoid cystic carcinoma: using whole-genome sequencing to inform clinical decision-making |
title_short | Personalized oncogenomic analysis of metastatic adenoid cystic carcinoma: using whole-genome sequencing to inform clinical decision-making |
title_sort | personalized oncogenomic analysis of metastatic adenoid cystic carcinoma: using whole-genome sequencing to inform clinical decision-making |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5880267/ https://www.ncbi.nlm.nih.gov/pubmed/29610392 http://dx.doi.org/10.1101/mcs.a002626 |
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