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Development and characterization of xenograft model systems for adenoid cystic carcinoma.

Moskaluk CA, Baras AS, Mancuso SA, Fan H, Davidson RJ, Dirks DC, Golden WL, Frierson HF - Lab. Invest. (2011)

Bottom Line: Adenoid cystic carcinoma (ACC) is one of the most common malignancies to arise in human salivary glands, and it also arises in the glandular tissue of other organ systems.As ACC is known to frequently contain a t(6;9) translocation that fuses the MYB and NFIB genes, fluorescence in situ hybridization (FISH) of 12 ACC xenograft models was performed that assayed MYB locus break-apart and MYB-NFIB locus fusion.The two related xenograft models (derived from primary and metastatic tumors, respectively, of the same human subject) were karyotyped, showing a t(1;6) translocation, suggesting MYB translocation to a novel fusion partner gene.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, University of Virginia, Charlottesville, VA 22908, USA. cam5p@virginia.edu

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Related in: MedlinePlus

Clustering of gene expression profiling dataA subset of xenograft tumors and samples of the corresponding human tumor from which they were derived were subjected to gene expression profiling on HU133 Plus 2.0 GeneChipsTM. Shown here is a heatmap of the 1271 probe sets that distinguish ACC tumors from normal salivary gland (NSG) tissue, and to the left of the heatmap, the graphical results of unsupervised clustering analysis of the expression profiles, using the furthest neighbor algorithm (complete linkage) with the Euclidean distance metric. The human tumors and the xenograft tumors cluster together and away from the NSG samples, with clear populations of differentially-regulated genes between the malignant and benign tissue samples. In almost every case, the xenograft tumor clusters most closely with the human tumor from which it was derived. The only exceptions were ACCX2 and 6, which were derived from primary and metastatic tumors from the same patient, in which the human samples and xenografts clustered closer to each other than to their related xenograft.
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Figure 2: Clustering of gene expression profiling dataA subset of xenograft tumors and samples of the corresponding human tumor from which they were derived were subjected to gene expression profiling on HU133 Plus 2.0 GeneChipsTM. Shown here is a heatmap of the 1271 probe sets that distinguish ACC tumors from normal salivary gland (NSG) tissue, and to the left of the heatmap, the graphical results of unsupervised clustering analysis of the expression profiles, using the furthest neighbor algorithm (complete linkage) with the Euclidean distance metric. The human tumors and the xenograft tumors cluster together and away from the NSG samples, with clear populations of differentially-regulated genes between the malignant and benign tissue samples. In almost every case, the xenograft tumor clusters most closely with the human tumor from which it was derived. The only exceptions were ACCX2 and 6, which were derived from primary and metastatic tumors from the same patient, in which the human samples and xenografts clustered closer to each other than to their related xenograft.

Mentions: In a broader survey of gene expression profiling, we analyzed samples of primary tumors, normal salivary gland (NSG) tissue, and xenografted tumors by oligonucleotide microarrays (HG-U133 plus 2.0 & HG-U133A, Affymetrix). From differential expression analysis between primary human ACC and normal salivary gland (NSG) tissue samples on the HG-U133A platform, 1271 probe sets were identified as differentially expressed (false discovery rate < 0.05 and minimum absolute difference greater than 100). Using this subset of differentially expressed genes in unsupervised clustering analysis of the xenograft tumors and human ACC samples, the result showed that in almost all circumstances the xenografted tumors clustered most closely to the human tumor sample from which they were derived (Figure 2). The only exception was in the case where a primary human tumor clustered most closely to a sample of a subsequent metastasis from the same subject (Donor #4). Notably, the xenograft models derived from these primary (ACCX2) and metastatic (ACCX6) tumor samples clustered closest to each other, and formed a separate clade with the human tumors from whence they were derived. Additionally, the xenografted tumors showed conserved differential expression when compared to NSG samples. Overall this analysis indicates that the xenograft tumors maintain durable gene expression profiles that closely resemble the human tumors from which they were derived, and that the foreign murine host milieu does not cause gene expression differences so profound that the xenografted tumors cluster away from their derivatives.


Development and characterization of xenograft model systems for adenoid cystic carcinoma.

Moskaluk CA, Baras AS, Mancuso SA, Fan H, Davidson RJ, Dirks DC, Golden WL, Frierson HF - Lab. Invest. (2011)

Clustering of gene expression profiling dataA subset of xenograft tumors and samples of the corresponding human tumor from which they were derived were subjected to gene expression profiling on HU133 Plus 2.0 GeneChipsTM. Shown here is a heatmap of the 1271 probe sets that distinguish ACC tumors from normal salivary gland (NSG) tissue, and to the left of the heatmap, the graphical results of unsupervised clustering analysis of the expression profiles, using the furthest neighbor algorithm (complete linkage) with the Euclidean distance metric. The human tumors and the xenograft tumors cluster together and away from the NSG samples, with clear populations of differentially-regulated genes between the malignant and benign tissue samples. In almost every case, the xenograft tumor clusters most closely with the human tumor from which it was derived. The only exceptions were ACCX2 and 6, which were derived from primary and metastatic tumors from the same patient, in which the human samples and xenografts clustered closer to each other than to their related xenograft.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4151120&req=5

Figure 2: Clustering of gene expression profiling dataA subset of xenograft tumors and samples of the corresponding human tumor from which they were derived were subjected to gene expression profiling on HU133 Plus 2.0 GeneChipsTM. Shown here is a heatmap of the 1271 probe sets that distinguish ACC tumors from normal salivary gland (NSG) tissue, and to the left of the heatmap, the graphical results of unsupervised clustering analysis of the expression profiles, using the furthest neighbor algorithm (complete linkage) with the Euclidean distance metric. The human tumors and the xenograft tumors cluster together and away from the NSG samples, with clear populations of differentially-regulated genes between the malignant and benign tissue samples. In almost every case, the xenograft tumor clusters most closely with the human tumor from which it was derived. The only exceptions were ACCX2 and 6, which were derived from primary and metastatic tumors from the same patient, in which the human samples and xenografts clustered closer to each other than to their related xenograft.
Mentions: In a broader survey of gene expression profiling, we analyzed samples of primary tumors, normal salivary gland (NSG) tissue, and xenografted tumors by oligonucleotide microarrays (HG-U133 plus 2.0 & HG-U133A, Affymetrix). From differential expression analysis between primary human ACC and normal salivary gland (NSG) tissue samples on the HG-U133A platform, 1271 probe sets were identified as differentially expressed (false discovery rate < 0.05 and minimum absolute difference greater than 100). Using this subset of differentially expressed genes in unsupervised clustering analysis of the xenograft tumors and human ACC samples, the result showed that in almost all circumstances the xenografted tumors clustered most closely to the human tumor sample from which they were derived (Figure 2). The only exception was in the case where a primary human tumor clustered most closely to a sample of a subsequent metastasis from the same subject (Donor #4). Notably, the xenograft models derived from these primary (ACCX2) and metastatic (ACCX6) tumor samples clustered closest to each other, and formed a separate clade with the human tumors from whence they were derived. Additionally, the xenografted tumors showed conserved differential expression when compared to NSG samples. Overall this analysis indicates that the xenograft tumors maintain durable gene expression profiles that closely resemble the human tumors from which they were derived, and that the foreign murine host milieu does not cause gene expression differences so profound that the xenografted tumors cluster away from their derivatives.

Bottom Line: Adenoid cystic carcinoma (ACC) is one of the most common malignancies to arise in human salivary glands, and it also arises in the glandular tissue of other organ systems.As ACC is known to frequently contain a t(6;9) translocation that fuses the MYB and NFIB genes, fluorescence in situ hybridization (FISH) of 12 ACC xenograft models was performed that assayed MYB locus break-apart and MYB-NFIB locus fusion.The two related xenograft models (derived from primary and metastatic tumors, respectively, of the same human subject) were karyotyped, showing a t(1;6) translocation, suggesting MYB translocation to a novel fusion partner gene.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, University of Virginia, Charlottesville, VA 22908, USA. cam5p@virginia.edu

Show MeSH
Related in: MedlinePlus