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Rearrangements, Exp...
Rearrangements, Expression, and Clinical Significance of MYB and MYBL1 in Adenoid Cystic Carcinoma: A Multi-Institutional Study
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- Persson, Marta, 1979 (author)
- Gothenburg University,Göteborgs universitet,Sahlgrenska Centrum för Cancerforskning (SCCR),Sahlgrenska Center for Cancer Research (SCCR)
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- Andersson, Mattias K, 1979 (author)
- Gothenburg University,Göteborgs universitet,Sahlgrenska Centrum för Cancerforskning (SCCR),Sahlgrenska Center for Cancer Research (SCCR)
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Mitani, Y. (author)
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Brandwein-Weber, M. S. (author)
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Frierson, H. F. (author)
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Moskaluk, C. (author)
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Fonseca, I. (author)
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Ferrarotto, R. (author)
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Boecker, W. (author)
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Loening, T. (author)
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El-Naggar, A. K. (author)
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- Stenman, Göran, 1953 (author)
- Gothenburg University,Göteborgs universitet,Sahlgrenska Centrum för Cancerforskning (SCCR),Sahlgrenska Center for Cancer Research (SCCR)
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(creator_code:org_t)
- 2022-07-28
- 2022
- English.
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In: Cancers. - : MDPI AG. - 2072-6694. ; 14:15
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https://doi.org/10.3...
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Abstract
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- Simple Summary Adenoid cystic carcinoma (ACC) is an aggressive glandular cancer with poor prognosis that preferentially occurs in the head and neck. The MYB and MYBL1 oncogenes are main oncogenic drivers, but the true frequency and clinical significance of these alterations are unclear. Here, we have used tissue microarrays to study these genes in a multi-institutional study of close to 400 ACCs, the largest study to date. We found alterations of MYB/MYBL1 in 78% of the cases and overexpression of the MYB/MYBL1 proteins in 93% of the cases. Importantly, we show that patients with loss of one part of the MYB gene and its neighboring sequences on chromosome 6 have a significantly shorter overall survival compared to those without loss. Our study provides new knowledge about the frequency and clinical significance of MYB/MYBL1 alterations and identifies genes with tumor suppressive functions on chromosome 6 that contribute to poor prognosis in ACC. Adenoid cystic carcinoma (ACC) is an aggressive head and neck malignancy characterized by a t (6;9) translocation resulting in an MYB-NFIB gene fusion or, more rarely, an MYBL1 fusion. The true frequency and clinical significance of these alterations are still unclear. Here, we have used tissue microarrays and analyzed 391 ACCs and 647 non-ACC salivary neoplasms to study the prevalence, expression, and clinical significance of MYB/MYBL1 alterations by FISH and immunohistochemistry. Alterations of MYB or MYBL1 were found in 78% of the cases, of which 62% had MYB alterations and 16% had MYBL1 rearrangements. Overexpression of MYB/MYBL1 oncoproteins was detected in 93% of the cases. MYB split signal, seen in 39% of the cases, was specific for ACC and not encountered in non-ACC salivary tumors. Loss of the 3 '-part of MYB was enriched in grade 3 tumors and was a significant independent prognostic biomarker for overall survival in multivariate analyses. We hypothesize that loss of the 3 '-part of MYB results from an unbalanced t(6;9) leading to an MYB-NFIB fusion with concomitant loss of the segment distal to the MYB breakpoint in 6q23.3. Our study provides new knowledge about the prevalence and clinical significance of MYB/MYBL1 alterations and indicates the presence of genes with tumor suppressive functions in 6q23.3-qter that contribute to poor prognosis and short overall survival in ACC.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Keyword
- MYB
- MYBL1
- adenoid cystic carcinoma
- prognostic biomarker
- FISH
- immunohistochemistry
- tumor suppressor gene
- salivary-gland
- tumor-suppressor
- lacrimal gland
- gene fusions
- nfib
- head
- neck
- chromosome
- deviations
- breast
- Oncology
Publication and Content Type
- ref (subject category)
- art (subject category)
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Cancers
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Persson, Marta, ...
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Andersson, Matti ...
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Mitani, Y.
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Brandwein-Weber, ...
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Frierson, H. F.
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Moskaluk, C.
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show more...
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Fonseca, I.
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Ferrarotto, R.
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Boecker, W.
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Loening, T.
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El-Naggar, A. K.
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Stenman, Göran, ...
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show less...
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- MEDICAL AND HEALTH SCIENCES
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Cancers
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University of Gothenburg