Integrated immunohistochemical and DNA copy number profiling analysis provides insight into the molecular pathogenesis of canine follicular lymphoma
| Autor: | K. Le Boedec, Matthew Breen, Luke B. Borst, Victor E. Valli, Rachael Thomas, Z. Demeter, Katherine Kennedy, Kuldeep Singh |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
General Veterinary medicine.diagnostic_test Follicular lymphoma Genome-wide association study Chromosomal translocation Biology medicine.disease Molecular biology Lymphoma Pathogenesis 03 medical and health sciences 030104 developmental biology 0302 clinical medicine 030220 oncology & carcinogenesis medicine Immunohistochemistry Comparative genomic hybridization Fluorescence in situ hybridization |
| Zdroj: | Veterinary and Comparative Oncology. 15:852-867 |
| ISSN: | 1476-5810 |
| DOI: | 10.1111/vco.12227 |
| Popis: | Follicular lymphomas (FLs) typically exhibit a chromosome translocation that induces constitutive expression of the anti-apoptotic bcl2 protein and accumulation of additional molecular defects. This rearrangement offers a promising therapeutic target, but its nature as a fundamental driver of FL pathogenesis remains unclear as 15% of cases lack the translocation. We performed an integrated immunohistochemical and genomic investigation of 10 naturally occurring FL cases from domestic dogs, showing that, as with human tumours, they exhibit marked heterogeneity in the frequency and intensity of bcl2 protein expression. Genomic copy number aberrations were infrequent and broadly consistent with those of other canine B-cell lymphoma subtypes. None of the canine FL specimens exhibited a rearrangement consistent with the hallmark translocation of human FL, despite their remarkable histomorphologic similarity. Parallel exploration of canine and human cases may reveal alternative tumour-initiating mechanisms other than BCL2 disruption, yielding a more complete definition of the molecular pathogenesis of FL. |
| Databáze: | OpenAIRE |
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