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| Status |
Public on Mar 13, 2015 |
| Title |
A unifying gene signature for adenoid cystic cancer identifies parallel MYB-dependent and MYB-independent therapeutic targets (mRNA) |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
MYB activation is proposed to underlie development of adenoid cystic cancer (ACC), an aggressive salivary gland tumor with no effective systemic treatments. To discover druggable targets for ACC, we performed global mRNA/miRNA analyses of 12 ACC with matched normal tissues, and compared these data with 14 mucoepidermoid carcinomas (MEC) and 11 salivary adenocarcinomas (ADC). We detected a unique ACC gene signature of 1160 mRNAs and 22 miRNAs. MYB was the top-scoring gene (18-fold induction), however we observed the same signature in ACC without detectable MYB gene rearrangements. We also found 4 ACC tumors (1 among our 12 cases and 3 from public databases) with negligible MYB expression that retained the same ACC mRNA signature including over-expression of extracellular matrix (ECM) genes. Integration of this signature with somatic mutational analyses suggests that NOTCH1 and RUNX1 participate with MYB to activate ECM elements including the VCAN/HAPLN1 complex. We observed that forced MYB-NFIB expression in human salivary gland cells alters cell morphology and cell adhesion in vitro and depletion of VCAN blocked tumor cell growth of a short-term ACC tumor culture. In summary, we identified a unique ACC signature with parallel MYB-dependent and independent biomarkers and identified VCAN/HAPLN1 complexes as a potential target.
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| Overall design |
A total 12 human salivary gland adenoid cystic cancer and 12 mathced normal adjacent tissues. The 12 tumor samples contains 8 MYB-NFIB fusion positive tumor samples and 4 MYB-NFIB fusion negative samples. One of the 4 fusion negative tumors did not have high MYB expression. This is a mRNA whole exome expression assay.
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| Contributor(s) |
Gao R, Cao C, Zhang M, Maria-Cecilia L, Yan Y, Chen Z, Mitani Y, Zhang L, Zajac-Kaye M, Liu B, Wu L, Renne R, Baker HV, El-Naggar A, Kaye FJ |
| Citation(s) |
25587024 |
| |
| Submission date |
Jul 23, 2014 |
| Last update date |
Jul 26, 2018 |
| Contact name |
Nicholas Navin |
| Organization name |
UT MD Anderson
|
| Street address |
6767Bertner AVE
|
| City |
Houston |
| State/province |
tx |
| ZIP/Postal code |
77030 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL6244 |
[HuGene-1_0-st] Affymetrix Human Gene 1.0 ST Array [transcript (gene) version] |
|
| Samples (24)
|
| GSM1443185 |
Fusion positive tumor; biological rep1 |
| GSM1443186 |
Fusion positive tumor; biological rep2 |
| GSM1443187 |
Match normal of fusion positive tumor; biological rep1 |
| GSM1443188 |
Match norma lof fusion positive tumor; biological rep2 |
| GSM1443189 |
Fusion negative tumor; biological rep1 |
| GSM1443190 |
Match normal of fusion negative tumor; biological rep1 |
| GSM1443192 |
Fusion negative tumor; biological rep2 |
| GSM1443193 |
Match normal of fusion negative tumor; biological rep2 |
| GSM1443194 |
Fusion negative tumor; biological rep3 |
| GSM1443195 |
Match normal of fusion negative tumor; biological rep3 |
| GSM1443196 |
Fusion positive tumor; biological rep3 |
| GSM1443197 |
Match norma of fusion positive tumor; biological rep3 |
| GSM1443198 |
Fusion negative tumor; biological rep4 |
| GSM1443199 |
Match normal of fusion negative tumor; biological rep4 |
| GSM1443200 |
Fusion positive tumor; biological rep4 |
| GSM1443201 |
Match normal of fusion positive tumor; biological rep4 |
| GSM1443203 |
Fusion positive tumor; biological rep5 |
| GSM1443204 |
Match normal of fusion positive tumor; biological rep5 |
| GSM1443205 |
Fusion positive tumor; biological rep6 |
| GSM1443206 |
Match normal of fusion positive tumor; biological rep6 |
| GSM1443207 |
Fusion positive tumor; biological rep7 |
| GSM1443208 |
Match normal of fusion positive tumor; biological rep7 |
| GSM1443209 |
Fusion positive tumor; biological rep8 |
| GSM1443210 |
Match normal of fusion positive tumor; biological rep8 |
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| This SubSeries is part of SuperSeries: |
| GSE59702 |
A unifying gene signature for adenoid cystic cancer identifies parallel MYB-dependent and MYB-independent therapeutic targets |
|
| Relations |
| BioProject |
PRJNA255982 |
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