Cargando…

Dominant Gene Expression Profiles Define Adenoid Cystic Carcinoma (ACC) from Different Tissues: Validation of a Gene Signature Classifier for Poor Survival in Salivary Gland ACC

SIMPLE SUMMARY: Adenoid cystic carcinoma (ACC) is a pathologically distinctive tumor that most often occurs in major or minor salivary glands, but can also occur in other tissues. We compared the gene expression profiles of ACC tumor samples from salivary gland, lacrimal gland, breast or skin. Despi...

Descripción completa

Detalles Bibliográficos
Autores principales: Brayer, Kathryn J., Kang, Huining, El-Naggar, Adel K., Andreasen, Simon, Homøe, Preben, Kiss, Katalin, Mikkelsen, Lauge, Heegaard, Steffen, Pelaez, Daniel, Moeyersoms, Acadia, Tse, David T., Guo, Yan, Lee, David Y., Ness, Scott A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10000625/
https://www.ncbi.nlm.nih.gov/pubmed/36900183
http://dx.doi.org/10.3390/cancers15051390
_version_ 1784903924941062144
author Brayer, Kathryn J.
Kang, Huining
El-Naggar, Adel K.
Andreasen, Simon
Homøe, Preben
Kiss, Katalin
Mikkelsen, Lauge
Heegaard, Steffen
Pelaez, Daniel
Moeyersoms, Acadia
Tse, David T.
Guo, Yan
Lee, David Y.
Ness, Scott A.
author_facet Brayer, Kathryn J.
Kang, Huining
El-Naggar, Adel K.
Andreasen, Simon
Homøe, Preben
Kiss, Katalin
Mikkelsen, Lauge
Heegaard, Steffen
Pelaez, Daniel
Moeyersoms, Acadia
Tse, David T.
Guo, Yan
Lee, David Y.
Ness, Scott A.
author_sort Brayer, Kathryn J.
collection PubMed
description SIMPLE SUMMARY: Adenoid cystic carcinoma (ACC) is a pathologically distinctive tumor that most often occurs in major or minor salivary glands, but can also occur in other tissues. We compared the gene expression profiles of ACC tumor samples from salivary gland, lacrimal gland, breast or skin. Despite their different tissues of origin, the ACC tumors displayed highly related patterns of gene expression. Indeed, gene expression patterns could not distinguish ACC tumors from different tissues, suggesting that genetic and epigenetic regulatory events induce a dominant ACC ‘phenotype’. We also used the new cohort of salivary gland ACC tumors to validate a gene expression biomarker developed with a previously analyzed cohort. The 49-gene classifier correctly identified 98% of the poor survival patients, validating the biomarker and suggesting that a clinical test should be developed so patients at highest risk of poor survival can be identified and provided additional treatment. ABSTRACT: Adenoid cystic carcinoma (ACC) is an aggressive malignancy that most often arises in salivary or lacrimal glands but can also occur in other tissues. We used optimized RNA-sequencing to analyze the transcriptomes of 113 ACC tumor samples from salivary gland, lacrimal gland, breast or skin. ACC tumors from different organs displayed remarkedly similar transcription profiles, and most harbored translocations in the MYB or MYBL1 genes, which encode oncogenic transcription factors that may induce dramatic genetic and epigenetic changes leading to a dominant ‘ACC phenotype’. Further analysis of the 56 salivary gland ACC tumors led to the identification of three distinct groups of patients, based on gene expression profiles, including one group with worse survival. We tested whether this new cohort could be used to validate a biomarker developed previously with a different set of 68 ACC tumor samples. Indeed, a 49-gene classifier developed with the earlier cohort correctly identified 98% of the poor survival patients from the new set, and a 14-gene classifier was almost as accurate. These validated biomarkers form a platform to identify and stratify high-risk ACC patients into clinical trials of targeted therapies for sustained clinical response.
format Online
Article
Text
id pubmed-10000625
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-100006252023-03-11 Dominant Gene Expression Profiles Define Adenoid Cystic Carcinoma (ACC) from Different Tissues: Validation of a Gene Signature Classifier for Poor Survival in Salivary Gland ACC Brayer, Kathryn J. Kang, Huining El-Naggar, Adel K. Andreasen, Simon Homøe, Preben Kiss, Katalin Mikkelsen, Lauge Heegaard, Steffen Pelaez, Daniel Moeyersoms, Acadia Tse, David T. Guo, Yan Lee, David Y. Ness, Scott A. Cancers (Basel) Article SIMPLE SUMMARY: Adenoid cystic carcinoma (ACC) is a pathologically distinctive tumor that most often occurs in major or minor salivary glands, but can also occur in other tissues. We compared the gene expression profiles of ACC tumor samples from salivary gland, lacrimal gland, breast or skin. Despite their different tissues of origin, the ACC tumors displayed highly related patterns of gene expression. Indeed, gene expression patterns could not distinguish ACC tumors from different tissues, suggesting that genetic and epigenetic regulatory events induce a dominant ACC ‘phenotype’. We also used the new cohort of salivary gland ACC tumors to validate a gene expression biomarker developed with a previously analyzed cohort. The 49-gene classifier correctly identified 98% of the poor survival patients, validating the biomarker and suggesting that a clinical test should be developed so patients at highest risk of poor survival can be identified and provided additional treatment. ABSTRACT: Adenoid cystic carcinoma (ACC) is an aggressive malignancy that most often arises in salivary or lacrimal glands but can also occur in other tissues. We used optimized RNA-sequencing to analyze the transcriptomes of 113 ACC tumor samples from salivary gland, lacrimal gland, breast or skin. ACC tumors from different organs displayed remarkedly similar transcription profiles, and most harbored translocations in the MYB or MYBL1 genes, which encode oncogenic transcription factors that may induce dramatic genetic and epigenetic changes leading to a dominant ‘ACC phenotype’. Further analysis of the 56 salivary gland ACC tumors led to the identification of three distinct groups of patients, based on gene expression profiles, including one group with worse survival. We tested whether this new cohort could be used to validate a biomarker developed previously with a different set of 68 ACC tumor samples. Indeed, a 49-gene classifier developed with the earlier cohort correctly identified 98% of the poor survival patients from the new set, and a 14-gene classifier was almost as accurate. These validated biomarkers form a platform to identify and stratify high-risk ACC patients into clinical trials of targeted therapies for sustained clinical response. MDPI 2023-02-22 /pmc/articles/PMC10000625/ /pubmed/36900183 http://dx.doi.org/10.3390/cancers15051390 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Brayer, Kathryn J.
Kang, Huining
El-Naggar, Adel K.
Andreasen, Simon
Homøe, Preben
Kiss, Katalin
Mikkelsen, Lauge
Heegaard, Steffen
Pelaez, Daniel
Moeyersoms, Acadia
Tse, David T.
Guo, Yan
Lee, David Y.
Ness, Scott A.
Dominant Gene Expression Profiles Define Adenoid Cystic Carcinoma (ACC) from Different Tissues: Validation of a Gene Signature Classifier for Poor Survival in Salivary Gland ACC
title Dominant Gene Expression Profiles Define Adenoid Cystic Carcinoma (ACC) from Different Tissues: Validation of a Gene Signature Classifier for Poor Survival in Salivary Gland ACC
title_full Dominant Gene Expression Profiles Define Adenoid Cystic Carcinoma (ACC) from Different Tissues: Validation of a Gene Signature Classifier for Poor Survival in Salivary Gland ACC
title_fullStr Dominant Gene Expression Profiles Define Adenoid Cystic Carcinoma (ACC) from Different Tissues: Validation of a Gene Signature Classifier for Poor Survival in Salivary Gland ACC
title_full_unstemmed Dominant Gene Expression Profiles Define Adenoid Cystic Carcinoma (ACC) from Different Tissues: Validation of a Gene Signature Classifier for Poor Survival in Salivary Gland ACC
title_short Dominant Gene Expression Profiles Define Adenoid Cystic Carcinoma (ACC) from Different Tissues: Validation of a Gene Signature Classifier for Poor Survival in Salivary Gland ACC
title_sort dominant gene expression profiles define adenoid cystic carcinoma (acc) from different tissues: validation of a gene signature classifier for poor survival in salivary gland acc
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10000625/
https://www.ncbi.nlm.nih.gov/pubmed/36900183
http://dx.doi.org/10.3390/cancers15051390
work_keys_str_mv AT brayerkathrynj dominantgeneexpressionprofilesdefineadenoidcysticcarcinomaaccfromdifferenttissuesvalidationofagenesignatureclassifierforpoorsurvivalinsalivaryglandacc
AT kanghuining dominantgeneexpressionprofilesdefineadenoidcysticcarcinomaaccfromdifferenttissuesvalidationofagenesignatureclassifierforpoorsurvivalinsalivaryglandacc
AT elnaggaradelk dominantgeneexpressionprofilesdefineadenoidcysticcarcinomaaccfromdifferenttissuesvalidationofagenesignatureclassifierforpoorsurvivalinsalivaryglandacc
AT andreasensimon dominantgeneexpressionprofilesdefineadenoidcysticcarcinomaaccfromdifferenttissuesvalidationofagenesignatureclassifierforpoorsurvivalinsalivaryglandacc
AT homøepreben dominantgeneexpressionprofilesdefineadenoidcysticcarcinomaaccfromdifferenttissuesvalidationofagenesignatureclassifierforpoorsurvivalinsalivaryglandacc
AT kisskatalin dominantgeneexpressionprofilesdefineadenoidcysticcarcinomaaccfromdifferenttissuesvalidationofagenesignatureclassifierforpoorsurvivalinsalivaryglandacc
AT mikkelsenlauge dominantgeneexpressionprofilesdefineadenoidcysticcarcinomaaccfromdifferenttissuesvalidationofagenesignatureclassifierforpoorsurvivalinsalivaryglandacc
AT heegaardsteffen dominantgeneexpressionprofilesdefineadenoidcysticcarcinomaaccfromdifferenttissuesvalidationofagenesignatureclassifierforpoorsurvivalinsalivaryglandacc
AT pelaezdaniel dominantgeneexpressionprofilesdefineadenoidcysticcarcinomaaccfromdifferenttissuesvalidationofagenesignatureclassifierforpoorsurvivalinsalivaryglandacc
AT moeyersomsacadia dominantgeneexpressionprofilesdefineadenoidcysticcarcinomaaccfromdifferenttissuesvalidationofagenesignatureclassifierforpoorsurvivalinsalivaryglandacc
AT tsedavidt dominantgeneexpressionprofilesdefineadenoidcysticcarcinomaaccfromdifferenttissuesvalidationofagenesignatureclassifierforpoorsurvivalinsalivaryglandacc
AT guoyan dominantgeneexpressionprofilesdefineadenoidcysticcarcinomaaccfromdifferenttissuesvalidationofagenesignatureclassifierforpoorsurvivalinsalivaryglandacc
AT leedavidy dominantgeneexpressionprofilesdefineadenoidcysticcarcinomaaccfromdifferenttissuesvalidationofagenesignatureclassifierforpoorsurvivalinsalivaryglandacc
AT nessscotta dominantgeneexpressionprofilesdefineadenoidcysticcarcinomaaccfromdifferenttissuesvalidationofagenesignatureclassifierforpoorsurvivalinsalivaryglandacc