PMID- 21709671 OWN - NLM STAT- MEDLINE DCOM- 20111122 LR - 20230216 IS - 1530-0307 (Electronic) IS - 0023-6837 (Print) IS - 0023-6837 (Linking) VI - 91 IP - 10 DP - 2011 Oct TI - Development and characterization of xenograft model systems for adenoid cystic carcinoma. PG - 1480-90 LID - 10.1038/labinvest.2011.105 [doi] AB - 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. To address the paucity of experimental model systems for this tumor type, we have undertaken a program of transplanting tissue samples of human ACC into immunodeficient nu/nu mice to create xenograft model systems. In 17 of 23 attempts (74%), xenograft tumors were successfully grown. In all cases, the histologic appearance of the donating tumor was recapitulated in the subsequent xenograft. Characterization of a subset of xenograft models by immunohistochemical biomarkers and by RNA transcript microarray analysis showed good fidelity in the recapitulation of gene expression patterns in the xenograft tumors compared with the human donor tumors. 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. Of 12 xenograft models, 11 (92%) revealed MYB locus rearrangement and 10 (83%) showed evidence of fusion of the MYB and NFIB loci. 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. Overall, our results indicate that ACC is amenable to xenografting and that ACC xenograft models recapitulate the molecular and morphologic characteristics of human tumors, suggesting utility as valid experimental and preclinical model systems for this disease. CI - (c) 2011 USCAP, Inc All rights reserved FAU - Moskaluk, Christopher A AU - Moskaluk CA AD - Department of Pathology, University of Virginia, Charlottesville, VA 22908, USA. cam5p@virginia.edu FAU - Baras, Alexander S AU - Baras AS FAU - Mancuso, Stefani A AU - Mancuso SA FAU - Fan, Hao AU - Fan H FAU - Davidson, Robert J AU - Davidson RJ FAU - Dirks, Dawn C AU - Dirks DC FAU - Golden, Wendy L AU - Golden WL FAU - Frierson, Henry F Jr AU - Frierson HF Jr LA - eng GR - P30 CA044579/CA/NCI NIH HHS/United States GR - R01 DE014694/DE/NIDCR NIH HHS/United States GR - RC1 DE020687/DE/NIDCR NIH HHS/United States GR - RC1-DE020687/DE/NIDCR NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20110627 PL - United States TA - Lab Invest JT - Laboratory investigation; a journal of technical methods and pathology JID - 0376617 RN - 0 (Biomarkers) RN - 0 (NFI Transcription Factors) RN - 0 (NFIB protein, human) RN - 63231-63-0 (RNA) SB - IM MH - Animals MH - Biomarkers/metabolism MH - Carcinoma, Adenoid Cystic/genetics/*metabolism/*pathology/secondary MH - Chromosome Mapping MH - *Disease Models, Animal MH - Gene Expression Profiling MH - Gene Fusion MH - Genes, myb MH - Humans MH - Immunohistochemistry MH - In Situ Hybridization, Fluorescence MH - Karyotyping MH - *Mice MH - Mice, Nude MH - Microarray Analysis MH - NFI Transcription Factors/genetics MH - Neoplasm Transplantation MH - RNA/metabolism MH - Salivary Gland Neoplasms/genetics/*metabolism/*pathology MH - Translocation, Genetic MH - *Transplantation, Heterologous PMC - PMC4151120 MID - NIHMS560283 EDAT- 2011/06/29 06:00 MHDA- 2011/12/13 00:00 PMCR- 2014/09/02 CRDT- 2011/06/29 06:00 PHST- 2011/06/29 06:00 [entrez] PHST- 2011/06/29 06:00 [pubmed] PHST- 2011/12/13 00:00 [medline] PHST- 2014/09/02 00:00 [pmc-release] AID - S0023-6837(22)02715-5 [pii] AID - 10.1038/labinvest.2011.105 [doi] PST - ppublish SO - Lab Invest. 2011 Oct;91(10):1480-90. doi: 10.1038/labinvest.2011.105. Epub 2011 Jun 27.