Dataset Information

N-Terminal Truncated Myb with New Transcriptional Activity Produced Through Use of an Alternative MYB Promoter in Salivary Gland Adenoid Cystic Carcinoma.

ABSTRACT: Adenoid cystic carcinoma (ACC) is an aggressive salivary gland tumor that frequently displays perineural invasion and is often associated with translocations or overexpression of the MYB oncogene. Detailed analyses of MYB transcripts from ACC patient samples revealed that ACC tumors utilize an alternative MYB promoter, which is rarely used in normal cells or other tumor types. The alternative promoter transcripts produce N-terminally truncated Myb proteins lacking a highly conserved and phosphorylated domain, which includes the pS11 epitope that is frequently used to detect Myb proteins. In RNA-seq assays, Myb isoforms lacking the N-terminal domain displayed unique transcriptional activities, regulating many genes differently than full-length Myb. Thus, a regulatory pathway unique to ACC activates the alternative MYB promoter, leading to the production of a truncated Myb protein with altered transcriptional activities. This could provide new therapeutic opportunities for ACC patients.

SUBMITTER: Frerich CA

PROVIDER: S-EPMC7016764 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

N-Terminal Truncated Myb with New Transcriptional Activity Produced Through Use of an Alternative MYB Promoter in Salivary Gland Adenoid Cystic Carcinoma.

Frerich Candace A CA Sedam Hailey N HN Kang Huining H Mitani Yoshitsugu Y El-Naggar Adel K AK Ness Scott A SA

Cancers 20191221 1

Adenoid cystic carcinoma (ACC) is an aggressive salivary gland tumor that frequently displays perineural invasion and is often associated with translocations or overexpression of the MYB oncogene. Detailed analyses of MYB transcripts from ACC patient samples revealed that ACC tumors utilize an alternative MYB promoter, which is rarely used in normal cells or other tumor types. The alternative promoter transcripts produce N-terminally truncated Myb proteins lacking a highly c ...[more]

PMID: 31877778

Similar Datasets

Project description:Adenoid cystic carcinoma (ACC) is a slow growing, but relentless cancer. Due to its rarity and lack of understanding of its molecular etiology, no standard chemotherapy for ACC currently exists and many patients suffer from recurrent and/or metastatic disease. As such, development of safe and effective therapies is imperative. To describe and summarize existing clinical trial studies and preclinical discoveries, we surveyed the PubMed on developmental therapeutics for ACC. Objective response rates to monotherapy with cytotoxic agents were approximately 10% with cisplatin, 5-FU, gemcitabine, mitoxantrone, epirubicin, vinorelbine and paclitaxel. The most studied combination therapies were cyclophosphamide-doxorubicin-cisplatin (CAP) and cisplatin-vinorelbine, with an objective response rate of 18-31%. Among molecularly targeted drugs, the most studied drugs are inhibitors targeting the vascular endothelial growth factor receptor (VEGFR) to inhibit tumor angiogenesis. Among those, lenvatinib and axitinib showed a relatively high objective response rate of 11-16% and 9-17%, respectively. Given high recurrence rates and chemoresistance of ACC, treatments targeting cancer stem cells (CSC), which function as tumor-initiating cells and drive chemoresistance, may be particularly valuable. CSC have been shown to be targetable via MYB, Notch1, p53 and epigenetic mechanisms. Myb overexpression is characteristic in ACC but was previously thought to present a difficult target due to its nature as a transcription factor. However, due to the development Myb-targeted inhibitors and an ongoing clinical trial of MYB-targeted cancer vaccine therapy, MYB is becoming an increasingly attractive therapeutic target. Drugs targeting NOTCH signaling demonstrated 5-17% response rate in phase I clinical trials. Within the field of epigenetics, treatment with PRMT5 inhibitors has shown 21% partial response rate in phase I clinical trial. Immunotherapies, such as PD-1 inhibitors, are also associated with CSC, but have not been effective against ACC. However, clinical trials of cancer vaccine therapies are actively being conducted. In addition to conventional chemotherapies and inhibitors of angiogenesis, the emergence of new therapies such as immunotherapy and those targeting cancer stemness is expected to bring clinical benefits to patients in the future.

Dataset Information

N-Terminal Truncated Myb with New Transcriptional Activity Produced Through Use of an Alternative MYB Promoter in Salivary Gland Adenoid Cystic Carcinoma.

Publications

N-Terminal Truncated Myb with New Transcriptional Activity Produced Through Use of an Alternative MYB Promoter in Salivary Gland Adenoid Cystic Carcinoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets