Abstract:
:Survival in high-risk neuroblastoma (HR-NB) patients remains poor despite multimodal treatment. We aimed to identify HR-NB patients with worse outcomes by analyzing the genomic instability derived from segmental chromosomal aberrations. We calculated 3 genomic instability indexes for primary tumor SNP array profiles from 127 HR-NB patients: (1) Copy number aberration burden (%gainslength+%losseslength), (2) copy number load (CNL) (%gainslength-%losseslength) and (3) net genomic load (NGL) (%gainsamount-%lossesamount). Tumors were classified according to positive or negative CNL and NGL genomic subtypes. The impact of the genomic instability indexes on overall survival (OS) was assessed with Cox regression. We identified 38% of HR-NB patients with poor 5-year OS. A negative CNL genomic background was related to poor prognosis in patients ≥18 months showing tumors with homogeneous MYCN amplification (9.5% survival probability, P < 0.05) and patients with non-MYCN amplified NB (18.8% survival probability related to >2.4% CNL, P < 0.01). A positive CNL genomic background was associated with worse outcome in patients with heterogeneous MYCN amplification (22.5% survival probability, P < 0.05). We conclude that characterizing a tumor genomic background according to predominance of genome gained or lost contributes toward improved outcome prediction and brings greater insight into the tumor biology of HR-NB patients.
journal_name
Neoplasiajournal_title
Neoplasia (New York, N.Y.)authors
Fernández-Blanco B,Berbegall AP,Martin-Vañó S,Castel V,Navarro S,Noguera Rdoi
10.1016/j.neo.2020.11.001subject
Has Abstractpub_date
2021-01-01 00:00:00pages
12-20issue
1eissn
1522-8002issn
1476-5586pii
S1476-5586(20)30169-Xjournal_volume
23pub_type
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