Genomic differences in benign and malignant follicular thyroid tumours using 1-Mb array-comparative genomic hybridisation

Currently there is a lack of objective markers that can reliably differentiate benign and malignant follicular thyroid tumours. Such markers are needed to avoid the morbidity and cost of diagnosing these lesions by a thyroid lobectomy and then a second operation to remove the remaining half of thyroid if cancer is found. The aim of this research was to look for genomic markers that might solve this important problem. Ethical approval for the project was obtained. DNA was extracted from formalin-fixed paraffin-embedded specimens and copy number analysed using an in-house produced 1-megabase genomic array by comparative genomic hybridization (1Mb-aCGH). Acceptable quality data were obtained in 25/26 (96 %) of adenomas and 17/28 (61 %) of carcinomas. Among the carcinomas, 11 were minimally invasive (MI), 5 widely invasive (WI) and there was one metastasis. Recurrent copy number changes distinguishing benign and malignant included +1p34.2-36.33, +1q, +13q12.11-14.3, +14q22.1-32.33, +20q and -22. +20q became more sensitive (36.4 %) for MI carcinomas, whereas +13q12.11-14.3 and +14q22.1-32.33 became more sensitive (66.7 %) for identifying WI cancers from adenomas. Only in the context of aneuploidy (3 adenomas, 3 MI, 3 WI) there were some specific copy number changes that could differentiate all aneuploid adenomas from carcinomas. This research is the first using 1Mb-aCGH to study benign and malignant follicular thyroid tumours. Overall, the incidence of any copy number changes is low, but there are a number of changes associated with different tumour types. Further research with a larger sample and better quality DNA will clarify these findings.