Geographical Mapping of a Multifocal Thyroid Tumour Using Genetic Alteration Analysis & MiRNA Profiling
ST Aherne, PC Smyth, RJ Flavin, SM Russell, KM Denning, J Li, SM Guenther, JJ O'Leary, OM Sheils. Trinity College Dublin, Dublin, Ireland; Applied Biosystems, Foster City, CA; St James's Hospital, Dublin, Ireland
Background: Papillary thyroid carcinoma (PTC) frequently presents as multiple tumour-foci within a single thyroid gland or pluriform, with synchronous tumours comprising different histological variants, raising questions regarding its clonality. Among genetic aberrations described in PTC, BRAF V600E mutation and ret/PTC activation occur most commonly. Several studies have investigated the genetic alteration status of multifocal thyroid tumours, with discordant results. To expand on the question of clonality the objective of this study was to examine disparate geographical and morphological areas from a single PTC for the presence of ret/PTC or BRAF mutations and correlate it with miRNA expression profiles.
Design: A multicentric PTC containing classic PTC, insular and anaplastic foci, & tumour cells adjacent to vascular invasion and lymphocytic infiltrate was examined for the presence of ret/PTC & BRAF mutations. Geographical data was correlated with expression profiles of 330 miRNAs. Hierarchical clustering analysis of the profiles, miRNA gene target prediction, & immunohistochemistry were also performed.
Results: Each morphological area proved negative for ret/PTC 1 rearrangement. Two distinct foci with classic morphology harboured the BRAF mutation. All other regions, including the insular and anaplastic were negative for the mutation. MiRNA profiles were found to distinguish tumours containing the BRAF mutation from the other tumour types, & differentiate between insular and anaplastic tumours. Profiles also included miRNAs previously discovered in this cancer, and miRNAs linked to various processes involved in tumour growth and proliferation.
Conclusions: The initial genetic alteration analysis indicated that pluriform PTC did not necessarily evolve from classic PTC progenitor foci. MiRNA profile analysis, however provided an interesting interpretation to the answer of the clonality question. The hierarchical clustering analysis indicated that the multiple foci may not have arisen due to the clonal metastasis of tumour cells or of independent mutational events, but perhaps both phenomena can occur simultaneously within the one tumour to enhance cancer progression. Putative gene targets were also obtained for the differentially regulated miRNAs raising the question as to the utility of these RNAs as either biomarkers or biological mediators.
Tuesday, March 10, 2009 1:00 PM
Poster Session IV # 79, Tuesday Afternoon