title: Using RB1 mutations to assess minimal residual disease in metastatic retinoblastoma.
abstract: To assess complete remission before subjecting nongermline metastatic retinoblastoma patients to an autologous peripheral stem cell transplant, we tested for patient-specific retinoblastoma tumor suppressor gene (RB1) mutant alleles in cerebrospinal fluid (CSF) and bone marrow. In 1 child with CSF and 1 with bone marrow metastases, allele-specific polymerase chain reaction (AS-PCR) detected the biallelic RB1 mutations specific to their tumors. The tumor of Child A was homozygous for R251X, and in Child B, it was homozygous for R358X. In Child A, the R251X mutation was detected in mutant controls diluted to 1:12,800 but not in CSF samples, corroborating clinical remission after chemotherapy. In Child B's bone marrow, AS-PCR for R358X was strongly positive at the detection of relapse, and subsequent bone marrow samples corroborated clinical remission after chemotherapy. No mutant tumor RB1 alleles were detected in their harvested peripheral blood stem cells. Both children were deemed suitable candidates for supralethal-dosage consolidation chemotherapy followed by autologous peripheral stem cell rescue of the bone marrow aimed at curing their metastatic retinoblastoma. When Child A recurred, the mutant tumor RB1 allele was detected 3.5 months before conventional pathology detected retinoblastoma tumor cells in the CSF. Assaying tumor-specific RB1 mutations complements cytological and immunohistochemical assessment of retinoblastoma involvement of CSF and bone marrow. Tumor cells can be detected in numbers lower than possible by conventional methods. An early diagnosis of relapse may allow an early institution of new therapy. A prospective international multicenter trial of the rare patients with metastatic retinoblastoma would assess the role of molecular monitoring in surveillance for minimal residual disease and recurrence.
authors.affiliation: Divisions of Hematology/Oncology, The Hospital for Sick Children, University of Toronto, 555 University Avenue, Toronto, Ontario, Canada.
authors.forename: Helen
authors.initials: H
authors.lastname: Dimaras
authors.forename: Diane
authors.initials: D
authors.lastname: Rushlow
authors.forename: William
authors.initials: W
authors.lastname: Halliday
authors.forename: John J
authors.initials: JJ
authors.lastname: Doyle
authors.forename: Paul
authors.initials: P
authors.lastname: Babyn
authors.forename: Esteban M
authors.initials: EM
authors.lastname: Abella
authors.forename: James
authors.initials: J
authors.lastname: Williams
authors.forename: Elise
authors.initials: E
authors.lastname: Héon
authors.forename: Brenda L
authors.initials: BL
authors.lastname: Gallie
authors.forename: Helen S L
authors.initials: HS
authors.lastname: Chan
mesh_terms: D001706:Biopsy; D001853:Bone Marrow / Q000473:pathology; D016026:Bone Marrow Transplantation; D001859:Bone Neoplasms / Q000473:pathology; D002555:Cerebrospinal Fluid / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D015353:Eye Enucleation; D005260:Female; D006801:Humans; D007223:Infant; D009154:Mutation; D009362:Neoplasm Metastasis / Q000235:genetics; D016133:Polymerase Chain Reaction; D011859:Radiography; D019572:Retinal Neoplasms / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D012175:Retinoblastoma / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D016160:Retinoblastoma Protein / Q000235:genetics*; D033581:Stem Cell Transplantation
chemical_list: D016160:Retinoblastoma Protein