Details

Autor(en) / Beteiligte

• Schieffer, Kathleen M
• Feldman, Alexander Z
• Kautto, Esko A
• McGrath, Sean
• Miller, Anthony R
• Hernandez-Gonzalez, Maria Elena
• LaHaye, Stephanie
• Miller, Katherine E
• Koboldt, Daniel C
• Brennan, Patrick
• Kelly, Benjamin
• Wetzel, Amy
• Agarwal, Vibhuti
• Shatara, Margaret
• Conley, Suzanne
• Rodriguez, Diana P
• Abu-Arja, Rolla
• Shaikhkhalil, Ala
• Snuderl, Matija
• Orr, Brent A
• Finlay, Jonathan L
• Osorio, Diana S
• Drapeau, Annie I
• Leonard, Jeffrey R
• Pierson, Christopher R
• White, Peter
• Magrini, Vincent
• Mardis, Elaine R
• Wilson, Richard K
• Cottrell, Catherine E
• Boué, Daniel R

Titel

Molecular classification of a complex structural rearrangement of the RB1 locus in an infant with sporadic, isolated, intracranial, sellar region retinoblastoma

Ist Teil von

• Acta neuropathologica communications, 2021-04, Vol.9 (1), p.61-61, Article 61

Ort / Verlag

England: BioMed Central Ltd

Erscheinungsjahr

2021

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• Retinoblastoma is a childhood cancer of the retina involving germline or somatic alterations of the RB Transcriptional Corepressor 1 gene, RB1. Rare cases of sellar-suprasellar region retinoblastoma without evidence of ocular or pineal tumors have been described. A nine-month-old male presented with a sellar-suprasellar region mass. Histopathology showed an embryonal tumor with focal Flexner-Wintersteiner-like rosettes and loss of retinoblastoma protein (RB1) expression by immunohistochemistry. DNA array-based methylation profiling confidently classified the tumor as pineoblastoma group A/intracranial retinoblastoma. The patient was subsequently enrolled on an institutional translational cancer research protocol and underwent comprehensive molecular profiling, including paired tumor/normal exome and genome sequencing and RNA-sequencing of the tumor. Additionally, Pacific Biosciences (PacBio) Single Molecule Real Time (SMRT) sequencing was performed from comparator normal and disease-involved tissue to resolve complex structural variations. RNA-sequencing revealed multiple fusions clustered within 13q14.1-q21.3, including a novel in-frame fusion of RB1-SIAH3 predicted to prematurely truncate the RB1 protein. SMRT sequencing revealed a complex structural rearrangement spanning 13q14.11-q31.3, including two somatic structural variants within intron 17 of RB1. These events corresponded to the RB1-SIAH3 fusion and a novel RB1 rearrangement expected to correlate with the complete absence of RB1 protein expression. Comprehensive molecular analysis, including DNA array-based methylation profiling and sequencing-based methodologies, were critical for classification and understanding the complex mechanism of RB1 inactivation in this diagnostically challenging tumor.