Array comparative genomic hybridization in retinoma and retinoblastoma tissues.
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'.
Sampieri
Katia
K
Medical Genetics, Department of Molecular Biology, University of Siena, Policlinico Le Scotte, Siena, Italy.
Amenduni
Mariangela
M
Papa
Filomena Tiziana
FT
Katzaki
Eleni
E
Mencarelli
Maria Antonietta
MA
Marozza
Annabella
A
Epistolato
Maria Carmela
MC
Toti
Paolo
P
Lazzi
Stefano
S
Bruttini
Mirella
M
De Filippis
Roberta
R
De Francesco
Sonia
S
Longo
Ilaria
I
Meloni
Ilaria
I
Mari
Francesca
F
Acquaviva
Antonio
A
Hadjistilianou
Theodora
T
Renieri
Alessandra
A
Ariani
Francesca
F
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*
D000888:Antibodies, Anti-Idiotypic; D016160:Retinoblastoma Protein