title: 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.
authors: Azienda Ospedaliero-Universitaria S. Maria della Misericordia, Udine, Italy.
authors: Nadia
authors: N
authors: Passon
authors: Azienda Ospedaliero-Universitaria S. Maria della Misericordia, Udine, Italy.
authors: Elisa
authors: E
authors: Bregant
authors: Dipartimento di Medicina Interna e Specialità Mediche, Università di Roma "Sapienza", Rome, Italy.
authors: Marialuisa
authors: M
authors: Sponziello
authors: Dipartimento di Medicina Interna e Specialità Mediche, Università di Roma "Sapienza", Rome, Italy.
authors: Maria
authors: M
authors: Dima
authors: Dipartimento di Medicina Interna e Specialità Mediche, Università di Roma "Sapienza", Rome, Italy.
authors: Francesca
authors: F
authors: Rosignolo
authors: Dipartimento di Medicina Interna e Specialità Mediche, Università di Roma "Sapienza", Rome, Italy.
authors: Cosimo
authors: C
authors: Durante
authors: Dipartimento di Scienze della Salute, Università di Catanzaro, Catanzaro, Italy.
authors: Marilena
authors: M
authors: Celano
authors: Dipartimento di Scienze della Salute, Università di Catanzaro, Catanzaro, Italy.
authors: Diego
authors: D
authors: Russo
authors: Dipartimento di Medicina Interna e Specialità Mediche, Università di Roma "Sapienza", Rome, Italy.
authors: Sebastiano
authors: S
authors: Filetti
authors: Azienda Ospedaliero-Universitaria S. Maria della Misericordia, Udine, Italy. giuseppe.damante@uniud.it.|Dipartimento di Scienze Mediche e Biologiche, Università di Udine, Piazzale Kolbe 4, 33100, Udine, Italy. giuseppe.damante@uniud.it.
authors: Giuseppe
authors: G
authors: Damante
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002277:Carcinoma / Q000235:genetics*; D002291:Carcinoma, Papillary; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D017384:Sequence Deletion; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics*; D055815:Young Adult
chemical_list: C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
keywords: CGH array; Papillary thyroid carcinoma; Somatic mutation