Neuroblastoma arises in early fetal development and its evolutionary duration predicts outcome

Abstract

Neuroblastoma, the most frequent solid tumor in infants, shows very diverse outcomes from spontaneous regression to fatal disease. When these different tumors originate and how they evolve are not known. Here we quantify the somatic evolution of neuroblastoma by deep whole-genome sequencing, molecular clock analysis and population-genetic modeling in a comprehensive cohort covering all subtypes. We find that tumors across the entire clinical spectrum begin to develop via aberrant mitoses as early as the first trimester of pregnancy. Neuroblastomas with favorable prognosis expand clonally after short evolution, whereas aggressive neuroblastomas show prolonged evolution during which they acquire telomere maintenance mechanisms. The initial aneuploidization events condition subsequent evolution, with aggressive neuroblastoma exhibiting early genomic instability. We find in the discovery cohort (n = 100), and validate in an independent cohort (n = 86), that the duration of evolution is an accurate predictor of outcome. Thus, insight into neuroblastoma evolution may prospectively guide treatment decisions.

RBM39 degrader invigorates natural killer cells to eradicate neuroblastoma despite cancer cell plasticity

“…(K) Sox10 labels the SCP cell population as the progenitors of neuroblasts and Chromaffin cells that are origin of neuroblastoma. Left shows the distinct cell populations in human adrenal medulla and the right shows the expression of Sox10 in each cell population, based on scRNA-seq analysis from the study 9 .…”

“…Arising in early fetal development 9 , neuroblastoma is an extracranial, embryonal tumor derived from the neural crest lineage, transformed by MYC oncogenes 10–13 . 50% of high-risk neuroblastomas have MYCN amplification, while the other half express high levels of C-MYC .…”

Global lineage evolution pattern of sars-cov-2 in Africa, America, Europe, and Asia: A comparative analysis of variant clusters and their relevance across continents

“…When analyzing their global patterns based on the clade classification of SARS-CoV-2 virus presented in Table 1 , evolutionary patterns of the SARS-CoV-2 virus emerge from the perspective of cancer evolution, we found similar trends have been observed in the SARS-CoV-2 virus evolution. [ 16 , 19 ] For example, G, GH, GR, GRY proceeded with neutral evolution while GK generally showed a typical branching evolution. In particular, GRA (omicron), which appears to be typical of punctuated evolution.…”

Conditional c-MYC activation in catecholaminergic cells drives distinct neuroendocrine tumors: neuroblastoma vs somatostatinoma

“…twice per week, and DFMO (Eflornithine HCl monohydrate) (Carbosynth LLC, Cat# FE11666) treatment was administered (2 g/L) in drinking water bottle to the indicated experimental groups until the end of the experiment. For all the animal studies, tumor sizes were measured daily by caliper 7 days after implantation, and tumor volume was calculated by length × width 2 × (π / 6). For survival studies, animals were monitored daily until the endpoint was reached, that is when the experimental animals had (1) tumor diameter that reached 2 cm; (2) tumor ulceration reaching 1 cm in diameter, or persistent bleeding as a result of ulceration; (3) a 20% loss of body weight; (4) breathing difficulty or (5) poor mobility.…”

“…Neuroblastoma is a solid tumor that arises from the aberrant growth of progeny of neural crest cells during early fetal development 1–3 . Tumors begin to develop via aberrant mitoses as early as the first trimester of pregnancy, with clonal evolution leading to either a favorable or an aggressive disease 2 . Neuroblastoma is the most common type of cancer in infancy and causes as much as 15% of childhood cancer mortality 4,5 .…”