Diana Bell1,2, Achim H Bell3, Jolanta Bondaruk1, Ehab Y Hanna2, Randall S Weber2. 1. Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas. 2. Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas. 3. Lone Star College, Houston, Texas.
Abstract
BACKGROUND: Adenoid cystic carcinoma (ACC), 1 of the most common salivary gland malignancies, arises from the intercalated ducts, which are composed of inner ductal epithelial cells and outer myoepithelial cells. The objective of this study was to determine the genomic subtypes of ACC with emphasis on dominant cell type to identify potential specific biomarkers for each subtype and to improve the understanding of this disease. METHODS: A whole-genome expression study was performed based on 42 primary salivary ACCs and 5 normal salivary glands. RNA from these specimens was subjected to expression profiling with RNA sequencing, and results were analyzed to identify transcripts in epithelial-dominant ACC (E-ACC), myoepithelial-dominant ACC (M-ACC), and all ACC that were expressed differentially compared with the transcripts in normal salivary tissue. RESULTS: In total, the authors identified 430 differentially expressed transcripts that were unique to E-ACC, 392 that were unique to M-ACC, and 424 that were common to both M-ACC and E-ACC. The sets of E-ACC-specific and M-ACC-specific transcripts were sufficiently large to define and differentiate E-ACC from M-ACC. Ingenuity pathway analysis identified known cancer-related genes for 60% of the E-ACC transcripts, 69% of the M-ACC transcripts, and 68% of the transcripts that were common in both E-ACC and M-ACC. Three sets of highly expressed candidate genes-distal-less homeobox 6 (DLX6) for E-ACC; protein keratin 16 (KRT16), SRY box 11 (SOX11), and v-myb avian myeloblastosis viral oncogene homolog (MYB) for M-ACC; and engrailed 1 (EN1) and statherin (STATH), which are common to both E-ACC and M-ACC)-were further validated at the protein level. CONCLUSIONS: The current results enabled the authors to identify novel potential therapeutic targets and biomarkers in E-ACC and M-ACC individually, with the implication that EN1, DLX6, and OTX1 (orthodenticle homeobox 1) are potential drivers of these cancers. Cancer 2016;122:1513-22.
BACKGROUND:Adenoid cystic carcinoma (ACC), 1 of the most common salivary gland malignancies, arises from the intercalated ducts, which are composed of inner ductal epithelial cells and outer myoepithelial cells. The objective of this study was to determine the genomic subtypes of ACC with emphasis on dominant cell type to identify potential specific biomarkers for each subtype and to improve the understanding of this disease. METHODS: A whole-genome expression study was performed based on 42 primary salivary ACCs and 5 normal salivary glands. RNA from these specimens was subjected to expression profiling with RNA sequencing, and results were analyzed to identify transcripts in epithelial-dominant ACC (E-ACC), myoepithelial-dominant ACC (M-ACC), and all ACC that were expressed differentially compared with the transcripts in normal salivary tissue. RESULTS: In total, the authors identified 430 differentially expressed transcripts that were unique to E-ACC, 392 that were unique to M-ACC, and 424 that were common to both M-ACC and E-ACC. The sets of E-ACC-specific and M-ACC-specific transcripts were sufficiently large to define and differentiate E-ACC from M-ACC. Ingenuity pathway analysis identified known cancer-related genes for 60% of the E-ACC transcripts, 69% of the M-ACC transcripts, and 68% of the transcripts that were common in both E-ACC and M-ACC. Three sets of highly expressed candidate genes-distal-less homeobox 6 (DLX6) for E-ACC; protein keratin 16 (KRT16), SRY box 11 (SOX11), and v-myb avian myeloblastosis viral oncogene homolog (MYB) for M-ACC; and engrailed 1 (EN1) and statherin (STATH), which are common to both E-ACC and M-ACC)-were further validated at the protein level. CONCLUSIONS: The current results enabled the authors to identify novel potential therapeutic targets and biomarkers in E-ACC and M-ACC individually, with the implication that EN1, DLX6, and OTX1 (orthodenticle homeobox 1) are potential drivers of these cancers. Cancer 2016;122:1513-22.
Authors: Achim H Bell; Franco DeMonte; Shaan M Raza; Laurence D Rhines; Claudio E Tatsui; Victor G Prieto; Gregory N Fuller; Diana Bell Journal: Virchows Arch Date: 2017-08-27 Impact factor: 4.064
Authors: Ehab Y Hanna; Ahmed S A Abdelmeguid; Dianna Roberts; Achim H Bell; Randal S Weber; Diana Bell Journal: Virchows Arch Date: 2017-10-23 Impact factor: 4.064
Authors: Alexandra G Evstafieva; Irina E Kovaleva; Maria S Shoshinova; Andrei V Budanov; Peter M Chumakov Journal: PLoS One Date: 2018-02-08 Impact factor: 3.240
Authors: Candace A Frerich; Kathryn J Brayer; Brandon M Painter; Huining Kang; Yoshitsugu Mitani; Adel K El-Naggar; Scott A Ness Journal: Oncotarget Date: 2017-12-23
Authors: Manik Chahal; Erin Pleasance; Jasleen Grewal; Eric Zhao; Tony Ng; Erin Chapman; Martin R Jones; Yaoqing Shen; Karen L Mungall; Melika Bonakdar; Gregory A Taylor; Yussanne Ma; Andrew J Mungall; Richard A Moore; Howard Lim; Daniel Renouf; Stephen Yip; Steven J M Jones; Marco A Marra; Janessa Laskin Journal: Cold Spring Harb Mol Case Stud Date: 2018-04-02
Authors: Renata Ferrarotto; Yoshitsugu Mitani; Daniel J McGrail; Kaiyi Li; Tatiana V Karpinets; Diana Bell; Steven J Frank; Xingzhi Song; Michael E Kupferman; Bin Liu; J Jack Lee; Bonnie S Glisson; Jianhua Zhang; Jon C Aster; Shiaw-Yih Lin; P Andrew Futreal; John V Heymach; Adel K El-Naggar Journal: Clin Cancer Res Date: 2020-11-10 Impact factor: 13.801