Genomic differences between retinoma and retinoblastoma.
BACKGROUND
Genomic copy number changes are involved in the multi-step process transforming normal retina in retinoblastoma after RB1 mutational events. Previous studies on retinoblastoma samples led to a multi-step model in which after two successive RB1 mutations, further genomic changes accompany malignancy: 1q32.1 gain is followed by 6p22 gain, that in turn is followed by 16q22 loss and 2p24.1 gain. Retinoma is a benign variant of retinoblastoma that was initially considered a tumor regression, but recent evidences suggest that it rather represents a pre-malignant lesion. Genetic studies on retinoma tissue have rarely been performed.


METHODS
We investigated by Real-Time qPCR, copy number changes of candidate genes located within the 4 hot-spot regions (MDM4 at 1q32.1, MYCN at 2p24.1, E2F3 at 6p22 and CDH11 at 16q22) in retina, retinoma and retinoblastoma tissues from two different patients.


RESULTS
Our results demonstrated that some copy number changes thought to belong to early (MDM4 gain) or late stage (MYCN and E2F3 gain) of retinoblastoma are already present in retinoma at the same (for MDM4) or at lower (for MYCN and E2F3) copy number variation respect to retinoblastoma. CDH11 copy number is not altered in the two retinoma samples, but gain is present in one of the two retinoblastomas.


CONCLUSIONS
Our results suggest that MDM4 gain may be involved in the early transition from normal retina to retinoma, while MYCN and E2F3 progressive gain may represent driving factors of tumor progression. These results also confirm the pre-malignant nature of retinoma.
Sampieri
Katia
K
Medical Genetics, Department of Molecular Biology, University of Siena, Siena, Italy.
Mencarelli
Maria Antonietta
MA
Epistolato
Maria Carmela
MC
Toti
Paolo
P
Lazzi
Stefano
S
Bruttini
Mirella
M
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
D015820:Cadherins / Q000235:genetics; D018797:Cell Cycle Proteins; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D050699:E2F3 Transcription Factor / Q000235:genetics; D005260:Female; D005451:Fluorescein Angiography; D005784:Gene Amplification; D005819:Genetic Markers / Q000235:genetics*; D015894:Genome, Human; D006801:Humans; D007834:Lasers; D008297:Male; D042282:Microdissection; D000071447:N-Myc Proto-Oncogene Protein; D009687:Nuclear Proteins / Q000235:genetics; D015513:Oncogene Proteins / Q000235:genetics; D016133:Polymerase Chain Reaction; D011230:Precancerous Conditions / Q000235:genetics* / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000235:genetics; D012160:Retina / Q000378:metabolism / Q000473:pathology*; D019572:Retinal Neoplasms / Q000235:genetics* / Q000473:pathology; D012175:Retinoblastoma / Q000235:genetics* / Q000473:pathology
D015820:Cadherins; D018797:Cell Cycle Proteins; D050699:E2F3 Transcription Factor; C098319:E2F3 protein, human; D005819:Genetic Markers; C482775:MDM4 protein, human; C459801:MYCN protein, human; D000071447:N-Myc Proto-Oncogene Protein; D009687:Nuclear Proteins; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; C086960:osteoblast cadherin