Recurrent Somatic Chromosomal Abnormalities in Relapsed Extraocular Retinoblastoma
Por:
Aschero MR, Francis JH, Ganiewich D, Gomez-Gonzalez S, Sampor C, Zugbi S, Ottaviani D, Lemelle L, Mena M, Winter U, Correa Llano G, Lamas G, Lubieniecki F, Szijan I, Mora J, Podhajcer O, Doz F, Radvanyi F, Abramson DH, Llera AS, Schaiquevich PS, Lavarino C and Chantada G
Publicada:
1 feb 2021
Ahead of Print:
8 feb 2021
Resumen:
Simple Summary
Relapse outside the eye of retinoblastoma (the most common eye cancer in children) is an uncommon event in developed countries, however it is the main cause of death in patients with retinoblastoma worldwide. The genomic features of this population are not known. We studied 23 cases from four countries and found a characteristic pattern in chromosomal copy number alterations that could help guide future clinical management of these patients.
Most reports about copy number alterations (CNA) in retinoblastoma relate to patients with intraocular disease and features of children with extraocular relapse remain unknown, so we aimed to describe the CNA in this population. We evaluated 23 patients and 27 specimens from 4 centers. Seventeen cases had extraocular relapse after initial enucleation and six cases after an initial preservation attempt. We performed an analysis of CNA and BCOR gene alteration by SNP array (Single Nucleotide Polymorfism array), whole-exome sequencing, IMPACT panel and CGH array (Array-based comparative genomic hybridization). All cases presented CNA at a higher prevalence than those reported in previously published studies for intraocular cases. CNA previously reported for intraocular retinoblastoma were found at a high frequency in our cohort: gains in 1q (69.5%), 2p (60.9%) and 6p (86.9%), and 16q loss (78.2%). Other, previously less-recognized, CNA were found including loss of 11q (34.8%), gain of 17q (56.5%), loss of 19q (30.4%) and BCOR alterations were present in 72.7% of our cases. A high number of CNA including 11q deletions, 17q gains, 19q loss, and BCOR alterations, are more common in extraocular retinoblastoma. Identification of these features may be correlated with a more aggressive tumor warranting consideration for patient management.
Filiaciones:
Aschero MR:
Pathology Service, Hospital de Pediatría JP Garrahan, Buenos Aires 1245, Argentina
National Scientific and Technical Research Council, CONICET, Buenos Aires 1425, Argentina
Francis JH:
Ophthalmic Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
Ganiewich D:
Laboratory of Molecular and Cellular Therapy, Instituto Leloir-Instituto de Investigaciones Bioquímicas de Buenos Aires (IIBBA), Buenos Aires 1405, Argentina
Gomez-Gonzalez S:
Developmental Tumor Biology Laboratory, Institut de Recerca Sant Joan de Déu, 08950 Barcelona, Spain
Sampor C:
Hematology-Oncology Service, Hospital de Pediatría JP Garrahan, Buenos Aires 1245, Argentina
Zugbi S:
National Scientific and Technical Research Council, CONICET, Buenos Aires 1425, Argentina
Innovative Treatments Unit, Hospital de Pediatría JP Garrahan, Buenos Aires 1245, Argentina
Ottaviani D:
University of Paris and Institut Curie (SIREDO Center: Care, Innovation and Reserach in pediatric, Adolescent and Young Adults Oncology), CNRS, UMR144, Equipe Labellisée Ligue Contre le Cancer, 75005 Paris, France
Lemelle L:
University of Paris and Institut Curie (SIREDO Center: Care, Innovation and Reserach in pediatric, Adolescent and Young Adults Oncology), CNRS, UMR144, Equipe Labellisée Ligue Contre le Cancer, 75005 Paris, France
Mena M:
Innovative Treatments Unit, Hospital de Pediatría JP Garrahan, Buenos Aires 1245, Argentina
Winter U:
Pathology Service, Hospital de Pediatría JP Garrahan, Buenos Aires 1245, Argentina
:
Pediatric Hematology and Oncology, Hospital Sant Joan de Déu, 08950 Barcelona, Spain
Lamas G:
Pathology Service, Hospital de Pediatría JP Garrahan, Buenos Aires 1245, Argentina
Lubieniecki F:
Pathology Service, Hospital de Pediatría JP Garrahan, Buenos Aires 1245, Argentina
Szijan I:
Genetic and Molecular Biology, University of Buenos Aires, Buenos Aires 1113, Argentina
Mora J:
Developmental Tumor Biology Laboratory, Institut de Recerca Sant Joan de Déu, 08950 Barcelona, Spain
Pediatric Hematology and Oncology, Hospital Sant Joan de Déu, 08950 Barcelona, Spain
Podhajcer O:
National Scientific and Technical Research Council, CONICET, Buenos Aires 1425, Argentina
Laboratory of Molecular and Cellular Therapy, Instituto Leloir-Instituto de Investigaciones Bioquímicas de Buenos Aires (IIBBA), Buenos Aires 1405, Argentina
Doz F:
University of Paris and Institut Curie (SIREDO Center: Care, Innovation and Reserach in pediatric, Adolescent and Young Adults Oncology), CNRS, UMR144, Equipe Labellisée Ligue Contre le Cancer, 75005 Paris, France
Radvanyi F:
University of Paris and Institut Curie (SIREDO Center: Care, Innovation and Reserach in pediatric, Adolescent and Young Adults Oncology), CNRS, UMR144, Equipe Labellisée Ligue Contre le Cancer, 75005 Paris, France
Abramson DH:
Ophthalmic Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
Llera AS:
National Scientific and Technical Research Council, CONICET, Buenos Aires 1425, Argentina
Laboratory of Molecular and Cellular Therapy, Instituto Leloir-Instituto de Investigaciones Bioquímicas de Buenos Aires (IIBBA), Buenos Aires 1405, Argentina
Schaiquevich PS:
National Scientific and Technical Research Council, CONICET, Buenos Aires 1425, Argentina
Innovative Treatments Unit, Hospital de Pediatría JP Garrahan, Buenos Aires 1245, Argentina
Lavarino C:
Developmental Tumor Biology Laboratory, Institut de Recerca Sant Joan de Déu, 08950 Barcelona, Spain
Pediatric Hematology and Oncology, Hospital Sant Joan de Déu, 08950 Barcelona, Spain
Chantada G:
National Scientific and Technical Research Council, CONICET, Buenos Aires 1425, Argentina
Pediatric Hematology and Oncology, Hospital Sant Joan de Déu, 08950 Barcelona, Spain
Green Submitted, gold
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