MYB, MYBL1, MYBL2 and NFIB gene alterations and MYC overexpression in salivary gland adenoid cystic carcinoma
| Autor: | Takayuki Murase, Ayako Masaki, Kosuke Saida, Nobuhiro Hanai, Shintaro Beppu, Yoshiyuki Iida, Kei Ijichi, Yasushi Yatabe, Hiroshi Inagaki, Kana Fujii, Kimihide Kusafuka, Yasuhisa Hasegawa, Hisashi Takino, Tetsuro Onitsuka |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Adult Male Histology Adenoid cystic carcinoma Genes myb Cell Cycle Proteins Kaplan-Meier Estimate Biology Translocation Genetic Pathology and Forensic Medicine Proto-Oncogene Proteins c-myc 03 medical and health sciences 0302 clinical medicine Proto-Oncogene Proteins medicine Biomarkers Tumor Humans MYB Gene Aged Proportional Hazards Models Antibody-dependent cell-mediated cytotoxicity Aged 80 and over Salivary gland General Medicine Middle Aged medicine.disease Salivary Gland Neoplasms Molecular biology Carcinoma Adenoid Cystic Oncogene Proteins v-myb Salivary Gland Adenoid Cystic Carcinoma NFI Transcription Factors 030104 developmental biology medicine.anatomical_structure NFIB 030220 oncology & carcinogenesis Cancer research Trans-Activators Female MYBL2 Gene |
| Zdroj: | Histopathology. 71(5) |
| ISSN: | 1365-2559 |
| Popis: | Aims Adenoid cystic carcinoma (AdCC) is one of the most common salivary gland malignancies and the long-term prognosis is poor. In this study, we examined alterations of AdCC-associated genes, MYB, MYBL1, MYBL2 and NFIB, and their target molecules, including MYC. The results were correlated to clinicopathological profile of the patients. Methods and results Using paraffin tumour sections from 33 cases of salivary gland AdCC, we performed a detailed fluorescence in-situ hybridization (FISH) analysis for gene splits and fusions of MYB, MYBL1, MYBL2 and NFIB. We found that 29 of 33 (88%) AdCC cases showed gene splits in either MYB, MYBL1 or NFIB. None of the cases showed an MYBL2 gene alteration. AdCCs were divided genetically into six gene groups, MYB–NFIB (n = 16), MYB–X (n = 4), MYBL1–NFIB (n = 2), MYBL1–X (n = 1), NFIB–X (n = 6) and gene-split-negative (n = 4). AdCC patients showing the MYB or MYBL1 gene splits were associated with microscopically positive surgical margins (P = 0.0148) and overexpression of MYC (P = 0.0164). MYC expression was detected in both ductal and myoepithelial tumour cells, and MYC overexpression was associated with shorter disease-free survival of the patients (P = 0.0268). Conclusions The present study suggests that (1) nearly 90% of AdCCs may have gene alterations of either MYB, MYBL1 or NFIB, suggesting the diagnostic utility of the FISH assay, (2) MYB or MYBL1 gene splits may be associated with local aggressiveness of the tumours and overexpression of MYC, which is one of the oncogenic MYB/MYBL1 targets and (3) MYC overexpression may be a risk factor for disease-free survival in AdCC. |
| Databáze: | OpenAIRE |
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