Adenoid cystic carcinomas of the salivary gland, lacrimal gland, and breast are morphologically and genetically similar but have distinct microRNA expression profiles

Simon Andreasen*, Qihua Tan, Tina Klitmøller Agander, Petr Steiner, Kristine Bjørndal, Estrid Høgdall, Stine Rosenkilde Larsen, Daiva Erentaite, Caroline Holkmann Olsen, Benedicte Parm Ulhøi, Sarah Linéa von Holstein, Irene Wessel, Steffen Heegaard, Preben Homøe

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Adenoid cystic carcinoma is among the most frequent malignancies in the salivary and lacrimal glands and has a grave prognosis characterized by frequent local recurrences, distant metastases, and tumor-related mortality. Conversely, adenoid cystic carcinoma of the breast is a rare type of triple-negative (estrogen and progesterone receptor, HER2) and basal-like carcinoma, which in contrast to other triple-negative and basal-like breast carcinomas has a very favorable prognosis. Irrespective of site, adenoid cystic carcinoma is characterized by gene fusions involving MYB, MYBL1, and NFIB, and the reason for the different clinical outcomes is unknown. In order to identify the molecular mechanisms underlying the discrepancy in clinical outcome, we characterized the phenotypic profiles, pattern of gene rearrangements, and global microRNA expression profiles of 64 salivary gland, 9 lacrimal gland, and 11 breast adenoid cystic carcinomas. All breast and lacrimal gland adenoid cystic carcinomas had triple-negative and basal-like phenotypes, while salivary gland tumors were indeterminate in 13% of cases. Aberrations in MYB and/or NFIB were found in the majority of cases in all three locations, whereas MYBL1 involvement was restricted to tumors in the salivary gland. Global microRNA expression profiling separated salivary and lacrimal gland adenoid cystic carcinoma from their respective normal glands but could not distinguish normal breast adenoid cystic carcinoma from normal breast tissue. Hierarchical clustering separated adenoid cystic carcinomas of salivary gland origin from those of the breast and placed lacrimal gland carcinomas in between these. Functional annotation of the microRNAs differentially expressed between salivary gland and breast adenoid cystic carcinoma showed these as regulating genes involved in metabolism, signal transduction, and genes involved in other cancers. In conclusion, microRNA dysregulation is the first class of molecules separating adenoid cystic carcinoma according to the site of origin. This highlights a novel venue for exploring the biology of adenoid cystic carcinoma.

Original languageEnglish
JournalModern Pathology
Volume31
Issue number8
Pages (from-to)1211–1225
ISSN0893-3952
DOIs
Publication statusPublished - Aug 2018

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Lacrimal Apparatus
Adenoid Cystic Carcinoma
MicroRNAs
Neoplasms
Glandular and Epithelial Neoplasms
Progesterone Receptors
Cluster Analysis

Cite this

Andreasen, Simon ; Tan, Qihua ; Agander, Tina Klitmøller ; Steiner, Petr ; Bjørndal, Kristine ; Høgdall, Estrid ; Larsen, Stine Rosenkilde ; Erentaite, Daiva ; Olsen, Caroline Holkmann ; Ulhøi, Benedicte Parm ; von Holstein, Sarah Linéa ; Wessel, Irene ; Heegaard, Steffen ; Homøe, Preben. / Adenoid cystic carcinomas of the salivary gland, lacrimal gland, and breast are morphologically and genetically similar but have distinct microRNA expression profiles. In: Modern Pathology. 2018 ; Vol. 31, No. 8. pp. 1211–1225.
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title = "Adenoid cystic carcinomas of the salivary gland, lacrimal gland, and breast are morphologically and genetically similar but have distinct microRNA expression profiles",
abstract = "Adenoid cystic carcinoma is among the most frequent malignancies in the salivary and lacrimal glands and has a grave prognosis characterized by frequent local recurrences, distant metastases, and tumor-related mortality. Conversely, adenoid cystic carcinoma of the breast is a rare type of triple-negative (estrogen and progesterone receptor, HER2) and basal-like carcinoma, which in contrast to other triple-negative and basal-like breast carcinomas has a very favorable prognosis. Irrespective of site, adenoid cystic carcinoma is characterized by gene fusions involving MYB, MYBL1, and NFIB, and the reason for the different clinical outcomes is unknown. In order to identify the molecular mechanisms underlying the discrepancy in clinical outcome, we characterized the phenotypic profiles, pattern of gene rearrangements, and global microRNA expression profiles of 64 salivary gland, 9 lacrimal gland, and 11 breast adenoid cystic carcinomas. All breast and lacrimal gland adenoid cystic carcinomas had triple-negative and basal-like phenotypes, while salivary gland tumors were indeterminate in 13{\%} of cases. Aberrations in MYB and/or NFIB were found in the majority of cases in all three locations, whereas MYBL1 involvement was restricted to tumors in the salivary gland. Global microRNA expression profiling separated salivary and lacrimal gland adenoid cystic carcinoma from their respective normal glands but could not distinguish normal breast adenoid cystic carcinoma from normal breast tissue. Hierarchical clustering separated adenoid cystic carcinomas of salivary gland origin from those of the breast and placed lacrimal gland carcinomas in between these. Functional annotation of the microRNAs differentially expressed between salivary gland and breast adenoid cystic carcinoma showed these as regulating genes involved in metabolism, signal transduction, and genes involved in other cancers. In conclusion, microRNA dysregulation is the first class of molecules separating adenoid cystic carcinoma according to the site of origin. This highlights a novel venue for exploring the biology of adenoid cystic carcinoma.",
author = "Simon Andreasen and Qihua Tan and Agander, {Tina Klitm{\o}ller} and Petr Steiner and Kristine Bj{\o}rndal and Estrid H{\o}gdall and Larsen, {Stine Rosenkilde} and Daiva Erentaite and Olsen, {Caroline Holkmann} and Ulh{\o}i, {Benedicte Parm} and {von Holstein}, {Sarah Lin{\'e}a} and Irene Wessel and Steffen Heegaard and Preben Hom{\o}e",
year = "2018",
month = "8",
doi = "10.1038/s41379-018-0005-y",
language = "English",
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Andreasen, S, Tan, Q, Agander, TK, Steiner, P, Bjørndal, K, Høgdall, E, Larsen, SR, Erentaite, D, Olsen, CH, Ulhøi, BP, von Holstein, SL, Wessel, I, Heegaard, S & Homøe, P 2018, 'Adenoid cystic carcinomas of the salivary gland, lacrimal gland, and breast are morphologically and genetically similar but have distinct microRNA expression profiles', Modern Pathology, vol. 31, no. 8, pp. 1211–1225. https://doi.org/10.1038/s41379-018-0005-y

Adenoid cystic carcinomas of the salivary gland, lacrimal gland, and breast are morphologically and genetically similar but have distinct microRNA expression profiles. / Andreasen, Simon; Tan, Qihua; Agander, Tina Klitmøller; Steiner, Petr; Bjørndal, Kristine; Høgdall, Estrid; Larsen, Stine Rosenkilde; Erentaite, Daiva; Olsen, Caroline Holkmann; Ulhøi, Benedicte Parm; von Holstein, Sarah Linéa; Wessel, Irene ; Heegaard, Steffen; Homøe, Preben.

In: Modern Pathology, Vol. 31, No. 8, 08.2018, p. 1211–1225.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Adenoid cystic carcinomas of the salivary gland, lacrimal gland, and breast are morphologically and genetically similar but have distinct microRNA expression profiles

AU - Andreasen, Simon

AU - Tan, Qihua

AU - Agander, Tina Klitmøller

AU - Steiner, Petr

AU - Bjørndal, Kristine

AU - Høgdall, Estrid

AU - Larsen, Stine Rosenkilde

AU - Erentaite, Daiva

AU - Olsen, Caroline Holkmann

AU - Ulhøi, Benedicte Parm

AU - von Holstein, Sarah Linéa

AU - Wessel, Irene

AU - Heegaard, Steffen

AU - Homøe, Preben

PY - 2018/8

Y1 - 2018/8

N2 - Adenoid cystic carcinoma is among the most frequent malignancies in the salivary and lacrimal glands and has a grave prognosis characterized by frequent local recurrences, distant metastases, and tumor-related mortality. Conversely, adenoid cystic carcinoma of the breast is a rare type of triple-negative (estrogen and progesterone receptor, HER2) and basal-like carcinoma, which in contrast to other triple-negative and basal-like breast carcinomas has a very favorable prognosis. Irrespective of site, adenoid cystic carcinoma is characterized by gene fusions involving MYB, MYBL1, and NFIB, and the reason for the different clinical outcomes is unknown. In order to identify the molecular mechanisms underlying the discrepancy in clinical outcome, we characterized the phenotypic profiles, pattern of gene rearrangements, and global microRNA expression profiles of 64 salivary gland, 9 lacrimal gland, and 11 breast adenoid cystic carcinomas. All breast and lacrimal gland adenoid cystic carcinomas had triple-negative and basal-like phenotypes, while salivary gland tumors were indeterminate in 13% of cases. Aberrations in MYB and/or NFIB were found in the majority of cases in all three locations, whereas MYBL1 involvement was restricted to tumors in the salivary gland. Global microRNA expression profiling separated salivary and lacrimal gland adenoid cystic carcinoma from their respective normal glands but could not distinguish normal breast adenoid cystic carcinoma from normal breast tissue. Hierarchical clustering separated adenoid cystic carcinomas of salivary gland origin from those of the breast and placed lacrimal gland carcinomas in between these. Functional annotation of the microRNAs differentially expressed between salivary gland and breast adenoid cystic carcinoma showed these as regulating genes involved in metabolism, signal transduction, and genes involved in other cancers. In conclusion, microRNA dysregulation is the first class of molecules separating adenoid cystic carcinoma according to the site of origin. This highlights a novel venue for exploring the biology of adenoid cystic carcinoma.

AB - Adenoid cystic carcinoma is among the most frequent malignancies in the salivary and lacrimal glands and has a grave prognosis characterized by frequent local recurrences, distant metastases, and tumor-related mortality. Conversely, adenoid cystic carcinoma of the breast is a rare type of triple-negative (estrogen and progesterone receptor, HER2) and basal-like carcinoma, which in contrast to other triple-negative and basal-like breast carcinomas has a very favorable prognosis. Irrespective of site, adenoid cystic carcinoma is characterized by gene fusions involving MYB, MYBL1, and NFIB, and the reason for the different clinical outcomes is unknown. In order to identify the molecular mechanisms underlying the discrepancy in clinical outcome, we characterized the phenotypic profiles, pattern of gene rearrangements, and global microRNA expression profiles of 64 salivary gland, 9 lacrimal gland, and 11 breast adenoid cystic carcinomas. All breast and lacrimal gland adenoid cystic carcinomas had triple-negative and basal-like phenotypes, while salivary gland tumors were indeterminate in 13% of cases. Aberrations in MYB and/or NFIB were found in the majority of cases in all three locations, whereas MYBL1 involvement was restricted to tumors in the salivary gland. Global microRNA expression profiling separated salivary and lacrimal gland adenoid cystic carcinoma from their respective normal glands but could not distinguish normal breast adenoid cystic carcinoma from normal breast tissue. Hierarchical clustering separated adenoid cystic carcinomas of salivary gland origin from those of the breast and placed lacrimal gland carcinomas in between these. Functional annotation of the microRNAs differentially expressed between salivary gland and breast adenoid cystic carcinoma showed these as regulating genes involved in metabolism, signal transduction, and genes involved in other cancers. In conclusion, microRNA dysregulation is the first class of molecules separating adenoid cystic carcinoma according to the site of origin. This highlights a novel venue for exploring the biology of adenoid cystic carcinoma.

U2 - 10.1038/s41379-018-0005-y

DO - 10.1038/s41379-018-0005-y

M3 - Journal article

VL - 31

SP - 1211

EP - 1225

JO - Modern Pathology

JF - Modern Pathology

SN - 0893-3952

IS - 8

ER -