Intra-Tumour Genetic Heterogeneity and Prognosis in High-Risk Neuroblastoma.

Autores de INCLIVA

• 

  María Amparo López Carrasco

  Autor

• 

  Susana Martín Vañó

  Autor

• 

  Samuel Navarro Fos

  Autor

• 

  Rosa Noguera Salva

  Autor

Participantes ajenos a INCLIVA

• Berbegall, Ana P
• Blanquer-Maceiras, Maite
• Castel, Victoria

Grupos y Plataformas de I+D+i

• Grupo de investigación en Enfermedades Metabólicas

  

  Established Researcher

  Herminia González Navarro

• Grupo de Investigación Translacional de Tumores Sólidos Pediátricos

  

  Leading Researcher

  Samuel Navarro Fos

Abstract

Spatial ITH is defined by genomic and biological variations within a tumour acquired by tumour cell evolution under diverse microenvironments, and its role in NB patient prognosis is understudied. In this work, we applied pangenomic techniques to detect chromosomal aberrations in at least two different areas of each tumour and/or in simultaneously obtained solid and liquid biopsies, detecting ITH in the genomic profile of almost 40% of HR-NB. ITH was better detected when comparing one or more tumour pieces and liquid biopsy (50%) than between different tumour pieces (21%). Interestingly, we found that patients with ITH analysed by pangenomic techniques had a significantly better survival rate that those with non-heterogeneous tumours, especially in cases without MYCN amplification. Moreover, all patients in the studied cohort with high ITH (defined as 50% or more genomic aberration differences between areas of a tumour or simultaneously obtained samples) survived after 48 months. These results clearly support analysing at least two solid tumour areas (separately or mixed) and liquid samples to provide more accurate genomic diagnosis, prognosis and therapy options in HR-NB.

Keywords

• MYCN amplification; SNPa; ctDNA; genomics; segmental chromosomal aberration; tumour microenvironment