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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

Examples of MYB-NFIB fusion FISHPanel A: The MYB gene locus on chromosome 6 and the NFIB gene locus on chromosome 9 are shown schematically, oriented to the centromeric (cen) and telomeric (tel) aspect of their respective chromosomes. The characteristic location of the t(6;9) translocation involved is shown by the crossed dotted lines. The location of the BAC clones used as FISH probes are shown above the MYB locus and below the NFIB locus, (drawn to scale) and colored to match the fluor used in the FISH assays. Panel B: ACCX22 displaying 1 yellow signal indicating a fusion of the MYB and NFIB loci. Separate unfused MYB and NFIB signals are also seen. Panel C: ACCX19 displaying 1 red/green signal indicating a fusion of the MYB and NFIB loci. Two additional separate green MYB signals are present, indicating duplication on one non-fused MYB locus. A separate red NFIB signal is also seen. Panel D: ACCX9 displaying 2 yellow signals consistent with a duplication of fused MYBNFIB loci. Panel E: ACCX2 displaying 2 separate green signals and 2 separate red signals indicating that the NFIB locus has not been fused to the MYB locus in this tumor.
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Figure 4: Examples of MYB-NFIB fusion FISHPanel A: The MYB gene locus on chromosome 6 and the NFIB gene locus on chromosome 9 are shown schematically, oriented to the centromeric (cen) and telomeric (tel) aspect of their respective chromosomes. The characteristic location of the t(6;9) translocation involved is shown by the crossed dotted lines. The location of the BAC clones used as FISH probes are shown above the MYB locus and below the NFIB locus, (drawn to scale) and colored to match the fluor used in the FISH assays. Panel B: ACCX22 displaying 1 yellow signal indicating a fusion of the MYB and NFIB loci. Separate unfused MYB and NFIB signals are also seen. Panel C: ACCX19 displaying 1 red/green signal indicating a fusion of the MYB and NFIB loci. Two additional separate green MYB signals are present, indicating duplication on one non-fused MYB locus. A separate red NFIB signal is also seen. Panel D: ACCX9 displaying 2 yellow signals consistent with a duplication of fused MYBNFIB loci. Panel E: ACCX2 displaying 2 separate green signals and 2 separate red signals indicating that the NFIB locus has not been fused to the MYB locus in this tumor.

Mentions: The same twelve xenograft cases described above were examined for the translocation of the NFIB locus on chromosome 9 to the MYB locus on chromosome 6, using the BAC probe centromeric to the MYB locus, RP11-104D9, labeled green with fluorescein and the BAC probe telomeric to the NFIB locus, RP11-170P19 labeled red with 5-ROX. 10 of the 12 xenograft models (83%) displayed a pairing of red and green signals, consistent with a MYB-NFIB gene fusion event (Table 4). Figure 4 shows representative examples of MYB-NFIB fusion FISH assays. The two xenograft models that did not show evidence of the t(6;9) translocation were related: ACCX2 and ACCX6, derived from the primary tumor and a metastatic tumor from the same patient. The fact that these xenografts had demonstrated findings in the break-apart FISH of a MYB locus rearrangement suggested an alternate chromosomal rearrangement event. There was only one discrepancy noted between the break-apart and fusion FISH analyses, and that was for ACCX22, in which the break-apart FISH showed two intact red/green probe pairs, but the fusion FISH was consistent with a MYB-NFIB locus fusion event.


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)

Examples of MYB-NFIB fusion FISHPanel A: The MYB gene locus on chromosome 6 and the NFIB gene locus on chromosome 9 are shown schematically, oriented to the centromeric (cen) and telomeric (tel) aspect of their respective chromosomes. The characteristic location of the t(6;9) translocation involved is shown by the crossed dotted lines. The location of the BAC clones used as FISH probes are shown above the MYB locus and below the NFIB locus, (drawn to scale) and colored to match the fluor used in the FISH assays. Panel B: ACCX22 displaying 1 yellow signal indicating a fusion of the MYB and NFIB loci. Separate unfused MYB and NFIB signals are also seen. Panel C: ACCX19 displaying 1 red/green signal indicating a fusion of the MYB and NFIB loci. Two additional separate green MYB signals are present, indicating duplication on one non-fused MYB locus. A separate red NFIB signal is also seen. Panel D: ACCX9 displaying 2 yellow signals consistent with a duplication of fused MYBNFIB loci. Panel E: ACCX2 displaying 2 separate green signals and 2 separate red signals indicating that the NFIB locus has not been fused to the MYB locus in this tumor.
© Copyright Policy
Related In: Results  -  Collection

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Figure 4: Examples of MYB-NFIB fusion FISHPanel A: The MYB gene locus on chromosome 6 and the NFIB gene locus on chromosome 9 are shown schematically, oriented to the centromeric (cen) and telomeric (tel) aspect of their respective chromosomes. The characteristic location of the t(6;9) translocation involved is shown by the crossed dotted lines. The location of the BAC clones used as FISH probes are shown above the MYB locus and below the NFIB locus, (drawn to scale) and colored to match the fluor used in the FISH assays. Panel B: ACCX22 displaying 1 yellow signal indicating a fusion of the MYB and NFIB loci. Separate unfused MYB and NFIB signals are also seen. Panel C: ACCX19 displaying 1 red/green signal indicating a fusion of the MYB and NFIB loci. Two additional separate green MYB signals are present, indicating duplication on one non-fused MYB locus. A separate red NFIB signal is also seen. Panel D: ACCX9 displaying 2 yellow signals consistent with a duplication of fused MYBNFIB loci. Panel E: ACCX2 displaying 2 separate green signals and 2 separate red signals indicating that the NFIB locus has not been fused to the MYB locus in this tumor.
Mentions: The same twelve xenograft cases described above were examined for the translocation of the NFIB locus on chromosome 9 to the MYB locus on chromosome 6, using the BAC probe centromeric to the MYB locus, RP11-104D9, labeled green with fluorescein and the BAC probe telomeric to the NFIB locus, RP11-170P19 labeled red with 5-ROX. 10 of the 12 xenograft models (83%) displayed a pairing of red and green signals, consistent with a MYB-NFIB gene fusion event (Table 4). Figure 4 shows representative examples of MYB-NFIB fusion FISH assays. The two xenograft models that did not show evidence of the t(6;9) translocation were related: ACCX2 and ACCX6, derived from the primary tumor and a metastatic tumor from the same patient. The fact that these xenografts had demonstrated findings in the break-apart FISH of a MYB locus rearrangement suggested an alternate chromosomal rearrangement event. There was only one discrepancy noted between the break-apart and fusion FISH analyses, and that was for ACCX22, in which the break-apart FISH showed two intact red/green probe pairs, but the fusion FISH was consistent with a MYB-NFIB locus fusion event.

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