Genetic analysis in retinoblastoma and peripheral blood correlation.
OBJECTIVE
To determine the importance of intratumoral genetic analysis in the diagnosis of germ-line mutations in patients with retinoblastoma. To underline the importance of performing these genetic tests in every case of retinoblastoma.


METHODS
Intratumoral genetic analysis of RB1 mutation was performed on 17 enucleated eyes that were non-responsive to conservative treatment. Patients had no family history of retinoblastoma, and lesions were always single. The identified mutations were then also studied in peripheral blood analysis.


RESULTS
There were 12 (70.6%) cases with positive results in intratumoral analysis. In 8 cases (47.1%) mutation of both RB1 alelli were detected, and in 4 (23.5%) cases only one allele was found mutated. In 5 patients (29.4%) no mutation was identified. In the first hit, mutations comprised 7 frameshift or nonsense and 2 splice, whereas in the second hit, one splice mutation, 2 nonsense and 8 loss of heterozygosity were identified. Among 6 patients where intratumoral analysis detected a single mutation associated with a loss of heterozygosity, the peripheral blood analysis was able to detect the same mutation in 3 cases (50%).


CONCLUSIONS
Intratumoral genetic analysis of sporadic retinoblastoma can detect germ-line mutations. These patients are at higher risk of bilateralization and development of second tumors or trilateral retinoblastoma. Genetic screening is recommended in every patient diagnosed with retinoblastoma.
Hospital Manises, Valencia, España. Electronic address: noeruizdelrio@yahoo.es.
N
N
Ruiz del Río
Hospital Universitario La Paz, Madrid, España.
J M
JM
Abelairas Gómez
Instituto de Investigaciones Biomédicas Alberto Sols, Madrid, España.
F J
FJ
Alonso García de la Rosa
Hospital Universitario La Paz, Madrid, España.
J M
JM
Peralta Calvo
Hospital La Mancha Centro, Ciudad Real, España.
A
A
de las Heras Martín
D000483:Alleles; D004252:DNA Mutational Analysis; D015353:Eye Enucleation; D005134:Eye Neoplasms / Q000097:blood / Q000737:chemistry / Q000235:genetics* / Q000601:surgery; D016161:Genes, Retinoblastoma; D005820:Genetic Testing; D018095:Germ-Line Mutation; D006801:Humans; D019656:Loss of Heterozygosity; D009154:Mutation; D009363:Neoplasm Proteins / Q000097:blood / Q000235:genetics; D009928:Organ Specificity; D012175:Retinoblastoma / Q000097:blood / Q000737:chemistry / Q000235:genetics* / Q000601:surgery; D056286:Retinoblastoma Binding Proteins / Q000032:analysis / Q000097:blood / Q000235:genetics; D016160:Retinoblastoma Protein / Q000097:blood / Q000235:genetics; D044767:Ubiquitin-Protein Ligases / Q000032:analysis / Q000097:blood / Q000235:genetics
D009363:Neoplasm Proteins; C000606393:RB1 protein, human; D056286:Retinoblastoma Binding Proteins; D016160:Retinoblastoma Protein; D044767:Ubiquitin-Protein Ligases
Cribado; Diagnosis; Diagnóstico; Gen RB1; Genetic test; RB1 gene; Retinoblastoma; Screening; Test genético