Somatic amplifications and deletions in genome of papillary thyroid carcinomas

Abstract

Somatic gene copy number variation contributes to tumor progression. Using comparative genomic hybridization (CGH) array, the presence of genomic imbalances was evaluated in a series of 27 papillary thyroid carcinomas (PTCs). To detect only somatic imbalances, for each sample, the reference DNA was from normal thyroid tissue of the same patient. The presence of the BRAF V600E mutation was also evaluated. Both amplifications and deletions showed an uneven distribution along the entire PTC cohort; amplifications were more frequent than deletions (mean values of 17.5 and 7.2, respectively). Number of aberration events was not even among samples, the majority of them occurring only in a small fraction of PTCs. Most frequent amplifications were detected at regions 2q35, 4q26, and 4q34.1, containing FN1, PDE5A, and GALNTL6 genes, respectively. Most frequent deletions occurred at regions 6q25.2, containing OPMR1 and IPCEF1 genes and 7q14.2, containing AOAH and ELMO1 genes. Amplification of FN1 and PDE5A genomic regions was confirmed by quantitative PCR. Frequency of amplifications and deletions was in relationship with clinical features and BRAF mutation status of tumor. In fact, according to the American Joint Committee on Cancer stage and American Thyroid Association (ATA) risk classification, amplifications are more frequent in higher risk samples, while deletions tend to prevail in the lower risk tumors. Analysis of single aberrations according to the ATA risk grouping shows that amplifications containing PDE5A, GALNTL6, DHRS3, and DOCK9 genes are significantly more frequent in the intermediate/high risk group than in the low risk group. Thus, our data would indicate that analysis of somatic genome aberrations by CGH array can be useful to identify additional prognostic variables.

Fibronectin-1 expression is increased in aggressive thyroid cancer and favors the migration and invasion of cancer cells

“…*p < 0.05, **p < 0.01, ***p < 0.001. ns, not significant. Center, 2015) and with a recent evidence of FN1 genomic amplifications found in a series of aggressive PTCs (Passon et al, 2015).…”

“…For each tumor, the risk of recurrence was classified as LR or IR in accordance with the 2015 ATA Guidelines for the Management of Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer (Haugen et al, 2016). BRAF mutational status was determined by Sanger sequencing, as previously described (Passon et al, 2015). PTC histotypes were determined by histopathological examination.…”

Expression of DOCK9 and DOCK11 Analyzed with Commercial Antibodies: Focus on Regulation of Mutually Exclusive First Exon Isoforms

“…In accordance with their function in cell plasticity, DOCK9 and DOCK11 could play roles in cancer and other pathologies. The abnormal expression of DOCK9 has been found in glioblastoma [ 18 ], papillary thyroid carcinoma [ 19 ], tuberculosis [ 20 ], prostate cancer [ 21 ], and pancreatic cancer [ 22 ], and of DOCK11 in testicular carcinoma [ 23 ]. The implementation of methods for studying the expression of DOCK9 and DOCK11 may help validate these alterations in large numbers of patients.…”

PDE5 Overexpression in Well-Differentiated Thyroid Carcinomas Is Associated with Lymph Node Metastasis

“…PDE5 inhibitors have also been used for therapeutic treatment [ 10 ]. Passon and colleagues have reported that the copy number of PDE5 is amplified in papillary thyroid cancer (PTC) [ 15 ]. Further, it was reported that variation in the copy number of PDE5 contributes to tumorigenesis and the development of PTC [ 16 ].…”