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Integrative genomic analysis of salivary duct carcinoma

Salivary duct carcinoma (SDC) is one of the most aggressive subtypes of salivary gland cancers. Conventional chemotherapy and/or radiation have shown only limited clinical efficacy in the treatment of recurrent or metastatic SDC. Currently, clinically approved targeted-therapeutics are not generally...

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Autores principales: Kim, Youngwook, Song, Sanghoon, Lee, Miran, Swatloski, Teresa, Kang, Joon Ho, Ko, Young-Hyeh, Park, Woong-Yang, Jeong, Han-Sin, Park, Keunchil
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7490354/
https://www.ncbi.nlm.nih.gov/pubmed/32929114
http://dx.doi.org/10.1038/s41598-020-72096-2
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author Kim, Youngwook
Song, Sanghoon
Lee, Miran
Swatloski, Teresa
Kang, Joon Ho
Ko, Young-Hyeh
Park, Woong-Yang
Jeong, Han-Sin
Park, Keunchil
author_facet Kim, Youngwook
Song, Sanghoon
Lee, Miran
Swatloski, Teresa
Kang, Joon Ho
Ko, Young-Hyeh
Park, Woong-Yang
Jeong, Han-Sin
Park, Keunchil
author_sort Kim, Youngwook
collection PubMed
description Salivary duct carcinoma (SDC) is one of the most aggressive subtypes of salivary gland cancers. Conventional chemotherapy and/or radiation have shown only limited clinical efficacy in the treatment of recurrent or metastatic SDC. Currently, clinically approved targeted-therapeutics are not generally applicable except in very limited cases, and there exists a strong need for the development of treatment against this unique tumor type. To further interrogate genomic features of SDC, we have conducted multi-omic profiling of the SDC to describe the genomic alterations prevalent in this disease. Whole-genome sequencing, whole exome-sequencing and transcriptome sequencing were performed on a discovery cohort of 10 SDC samples. Targeted genomic profiling was performed in additional 32 SDC samples to support the findings obtained from the original discovery cohort. The cancer cohort was characterized by an average mutation burden of 85 somatic exonic mutations per tumor sample. The cohort harbored a mutational signature of BRCA and APOBEC/AID. Several genes, including TP53, RB1, SMAD4, HRAS, APC, PIK3CA and GNAQ were recurrently somatically altered in SDC. A novel fusion gene, generated by genomic rearrangement, MYB-NHSL1, was also noted. Our findings represent a significant layer in the systematic understanding of potentially clinically useful genomic and molecular targets for a subset of recurrent/metastatic SDC.
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spelling pubmed-74903542020-09-16 Integrative genomic analysis of salivary duct carcinoma Kim, Youngwook Song, Sanghoon Lee, Miran Swatloski, Teresa Kang, Joon Ho Ko, Young-Hyeh Park, Woong-Yang Jeong, Han-Sin Park, Keunchil Sci Rep Article Salivary duct carcinoma (SDC) is one of the most aggressive subtypes of salivary gland cancers. Conventional chemotherapy and/or radiation have shown only limited clinical efficacy in the treatment of recurrent or metastatic SDC. Currently, clinically approved targeted-therapeutics are not generally applicable except in very limited cases, and there exists a strong need for the development of treatment against this unique tumor type. To further interrogate genomic features of SDC, we have conducted multi-omic profiling of the SDC to describe the genomic alterations prevalent in this disease. Whole-genome sequencing, whole exome-sequencing and transcriptome sequencing were performed on a discovery cohort of 10 SDC samples. Targeted genomic profiling was performed in additional 32 SDC samples to support the findings obtained from the original discovery cohort. The cancer cohort was characterized by an average mutation burden of 85 somatic exonic mutations per tumor sample. The cohort harbored a mutational signature of BRCA and APOBEC/AID. Several genes, including TP53, RB1, SMAD4, HRAS, APC, PIK3CA and GNAQ were recurrently somatically altered in SDC. A novel fusion gene, generated by genomic rearrangement, MYB-NHSL1, was also noted. Our findings represent a significant layer in the systematic understanding of potentially clinically useful genomic and molecular targets for a subset of recurrent/metastatic SDC. Nature Publishing Group UK 2020-09-14 /pmc/articles/PMC7490354/ /pubmed/32929114 http://dx.doi.org/10.1038/s41598-020-72096-2 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Kim, Youngwook
Song, Sanghoon
Lee, Miran
Swatloski, Teresa
Kang, Joon Ho
Ko, Young-Hyeh
Park, Woong-Yang
Jeong, Han-Sin
Park, Keunchil
Integrative genomic analysis of salivary duct carcinoma
title Integrative genomic analysis of salivary duct carcinoma
title_full Integrative genomic analysis of salivary duct carcinoma
title_fullStr Integrative genomic analysis of salivary duct carcinoma
title_full_unstemmed Integrative genomic analysis of salivary duct carcinoma
title_short Integrative genomic analysis of salivary duct carcinoma
title_sort integrative genomic analysis of salivary duct carcinoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7490354/
https://www.ncbi.nlm.nih.gov/pubmed/32929114
http://dx.doi.org/10.1038/s41598-020-72096-2
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