Molecular analysis distinguishes metastatic disease from second cancers in patients with retinoblastoma.
The pediatric ocular tumor retinoblastoma readily metastasizes, but these lesions can masquerade as histologically similar pediatric small round blue cell tumors. Since 98% of retinoblastomas have RB1 mutations and a characteristic genomic copy number "signature", genetic analysis is an appealing adjunct to histopathology to distinguish retinoblastoma metastasis from second primary cancer in retinoblastoma patients. Here, we describe such an approach in two retinoblastoma cases. In patient one, allele-specific (AS)-PCR for a somatic nonsense mutation confirmed that a temple mass was metastatic retinoblastoma. In a second patient, a rib mass shared somatic copy number gains and losses with the primary tumor. For definitive diagnosis, however, an RB1 mutation was needed, but heterozygous promoter→exon 11 deletion was the only RB1 mutation detected in the primary tumor. We used a novel application of inverse PCR to identify the deletion breakpoint. Subsequently, AS-PCR designed for the breakpoint confirmed that the rib mass was metastatic retinoblastoma. These cases demonstrate that personalized molecular testing can confirm retinoblastoma metastases and rule out a second primary cancer, thereby helping to direct the clinical management.
Impact Genetics, Bowmanville, Ontario L1C 3K5, Canada.
Hilary
H
Racher
Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada; Ophthalmology Department, Faculty of Medicine, University of Alexandria, Alexandria, Egypt.
Sameh
S
Soliman
Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta T2N 4N1, Canada.
Bob
B
Argiropoulos
Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada.
Helen S L
HS
Chan
Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada.
Brenda L
BL
Gallie
Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta T2N 4N1, Canada.
Renée
R
Perrier
Impact Genetics, Bowmanville, Ontario L1C 3K5, Canada.
Donco
D
Matevski
Impact Genetics, Bowmanville, Ontario L1C 3K5, Canada.
Diane
D
Rushlow
Impact Genetics, Bowmanville, Ontario L1C 3K5, Canada.
Beata
B
Piovesan
Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada.
Furqan
F
Shaikh
Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada.
Heather
H
MacDonald
Eugene and Marilyn Glick Eye Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA. Electronic address: tcorson@iu.edu.
Timothy W
TW
Corson
D002675:Child, Preschool; D019457:Chromosome Breakage; D018389:Codon, Nonsense; D003937:Diagnosis, Differential; D017809:Fatal Outcome; D005260:Female; D018628:Gene Dosage; D006801:Humans; D007223:Infant; D008297:Male; D009362:Neoplasm Metastasis; D016609:Neoplasms, Second Primary / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods*; D019572:Retinal Neoplasms / Q000235:genetics*; D012175:Retinoblastoma / Q000235:genetics*; D056286:Retinoblastoma Binding Proteins / Q000235:genetics*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
D018389:Codon, Nonsense; C000606393:RB1 protein, human; D056286:Retinoblastoma Binding Proteins; D044767:Ubiquitin-Protein Ligases
Retinoblastoma; differential diagnosis; inverse PCR; metastasis; mutation detection; second primary tumor