Ir para o conteúdo principal

Escrever uma avaliação PREreview

TMS: A DNA-Only Oxidative Damage Repair Signature for Risk Stratification of 1–2 Year Neuroblastoma

Publicado
Servidor
Preprints.org
DOI
10.20944/preprints202610.1940.v1

Background: Neuroblastoma (NBL) prognosis relies on clinical-molecular features that leave the 1-2 year age window—a challenging gray zone—poorly resolved. We developed a DNA-only trinucleotide mutation spectrum (TMS) signature to address this gap.Procedure: We trained TMS using lasso-penalized Cox regression on the OpenPedCan NBL MAF cohort (n=781), validated in TARGET (n=220) and GMKF (n=93) within the 1-2 year window, and compared against MYCN, mutation count, and RNA quality.Results: TMS captures a C>A/G>T-dominated oxidative damage spectrum, with ATC>C>A selected in 100/100 stability iterations. TMS_z correlated with oxidative repair genes, antioxidant genes, and C>A mutation burden (Spearman r=0.744). The prognostic effect was age-dependent, peaking at 1-2 years (1yr: HR=1.70, P=3.3e-5; 2yr: HR=1.47, P=9.0e-7; interaction P=3.4e-6). A threshold, TMS_z > 0.5, stratified patients (HR=3.13, 95% CI 2.10-4.66, P=1.9e-8; OR=5.09, P=1.2e-7), validated in TARGET (HR=2.96, P=4.0e-7) and directionally consistent in GMKF (HR=2.03, P=0.37). TMS remained significant after adjusting for MYCN (HR=3.65, P=0.0093) and mutation count (HR=1.73, P=2.2e-9), though partially overlapping with RNA quality axes (per-SD HR=1.32, P=0.063).Conclusions: TMS is a simple, DNA-only prognostic tool for 1-2 year NBL, providing MYCN- and mutation-count-independent risk stratification. Its DNA-only nature makes it applicable to FFPE and resource-limited settings.

Você pode escrever uma avaliação PREreview de TMS: A DNA-Only Oxidative Damage Repair Signature for Risk Stratification of 1–2 Year Neuroblastoma. Uma avaliação PREreview é uma avaliação de um preprint e pode variar de algumas frases a um parecer extenso, semelhante a um parecer de revisão por pares realizado por periódicos.

Antes de começar

We will ask you to log in with your ORCID iD. If you don’t have an iD, you can create one.

What is an ORCID iD?

An ORCID iD is a unique identifier that distinguishes you from everyone with the same or similar name.

Começar agora