title: Array comparative genomic hybridization in retinoma and retinoblastoma tissues.
abstract: In retinoblastoma, two RB1 mutations are necessary for tumor development. Recurrent genomic rearrangements may represent subsequent events required for retinoblastoma progression. Array-comparative genomic hybridization was carried out in 18 eye samples, 10 from bilateral and eight from unilateral retinoblastoma patients. Two unilateral cases also showed areas of retinoma. The most frequent imbalance in retinoblastomas was 6p gain (40%), followed by gains at 1q12-q25.3, 2p24.3-p24.2, 9q22.2, and 9q33.1 and losses at 11q24.3, 13q13.2-q22.3, and 16q12.1-q21. Bilateral cases showed a lower number of imbalances than unilateral cases (P = 0.002). Unilateral cases were divided into low-level (< or = 4) and high-level (> or = 7) chromosomal instability groups. The first group presented with younger age at diagnosis (mean 511 days) compared with the second group (mean 1606 days). In one retinoma case ophthalmoscopically diagnosed as a benign lesion no rearrangements were detected, whereas the adjacent retinoblastoma displayed seven aberrations. The other retinoma case identified by retrospective histopathological examination shared three rearrangements with the adjacent retinoblastoma. Two other gene-free rearrangements were retinoma specific. One rearrangement, dup5p, was retinoblastoma specific and included the SKP2 gene. Genomic profiling indicated that the first retinoma was a pretumoral lesion, whereas the other represents a subclone of cells bearing 'benign' rearrangements overwhelmed by another subclone presenting aberrations with higher 'oncogenic' potential. In summary, the present study shows that bilateral and unilateral retinoblastoma have different chromosomal instability that correlates with the age of tumor onset in unilateral cases. This is the first report of genomic profiling in retinoma tissue, shedding light on the different nature of lesions named 'retinoma'.
authors.affiliation: Medical Genetics, Department of Molecular Biology, University of Siena, Policlinico Le Scotte, Siena, Italy.
authors.forename: Katia
authors.initials: K
authors.lastname: Sampieri
authors.forename: Mariangela
authors.initials: M
authors.lastname: Amenduni
authors.forename: Filomena Tiziana
authors.initials: FT
authors.lastname: Papa
authors.forename: Eleni
authors.initials: E
authors.lastname: Katzaki
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: Mencarelli
authors.forename: Annabella
authors.initials: A
authors.lastname: Marozza
authors.forename: Maria Carmela
authors.initials: MC
authors.lastname: Epistolato
authors.forename: Paolo
authors.initials: P
authors.lastname: Toti
authors.forename: Stefano
authors.initials: S
authors.lastname: Lazzi
authors.forename: Mirella
authors.initials: M
authors.lastname: Bruttini
authors.forename: Roberta
authors.initials: R
authors.lastname: De Filippis
authors.forename: Sonia
authors.initials: S
authors.lastname: De Francesco
authors.forename: Ilaria
authors.initials: I
authors.lastname: Longo
authors.forename: Ilaria
authors.initials: I
authors.lastname: Meloni
authors.forename: Francesca
authors.initials: F
authors.lastname: Mari
authors.forename: Antonio
authors.initials: A
authors.lastname: Acquaviva
authors.forename: Theodora
authors.initials: T
authors.lastname: Hadjistilianou
authors.forename: Alessandra
authors.initials: A
authors.lastname: Renieri
authors.forename: Francesca
authors.initials: F
authors.lastname: Ariani
mesh_terms: D017668:Age of Onset; D000888:Antibodies, Anti-Idiotypic; D002675:Child, Preschool; D055028:Comparative Genomic Hybridization; D004252:DNA Mutational Analysis; D016161:Genes, Retinoblastoma; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007223:Infant; D007834:Lasers; D042282:Microdissection; D009154:Mutation; D019572:Retinal Neoplasms / Q000235:genetics* / Q000473:pathology; D012175:Retinoblastoma / Q000235:genetics* / Q000473:pathology; D016160:Retinoblastoma Protein / Q000235:genetics*
chemical_list: D000888:Antibodies, Anti-Idiotypic; D016160:Retinoblastoma Protein