López-Carrasco Amparo, Berbegall Ana P, Martín-Vañó Susana, Blanquer-Maceiras Maite, Castel Victoria, Navarro Samuel, Noguera Rosa
Department of Pathology, Medical School, University of Valencia-INCLIVA, 46010 Valencia, Spain.
CIBER of Cancer (CIBERONC), 28029 Madrid, Spain.
Cancers (Basel). 2021 Oct 15;13(20):5173. doi: 10.3390/cancers13205173.
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 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.
空间肿瘤内异质性由肿瘤细胞在不同微环境下进化所获得的肿瘤内基因组和生物学变异所定义，其在神经母细胞瘤（NB）患者预后中的作用尚未得到充分研究。在这项工作中，我们应用泛基因组技术检测每个肿瘤至少两个不同区域和/或同时获取的实体和液体活检样本中的染色体畸变，在近40%的高危神经母细胞瘤（HR-NB）基因组图谱中检测到肿瘤内异质性。与比较不同肿瘤块之间（21%）相比，比较一个或多个肿瘤块与液体活检样本时（50%）能更好地检测到肿瘤内异质性。有趣的是，我们发现通过泛基因组技术分析具有肿瘤内异质性的患者的生存率明显高于肿瘤无异质性的患者，尤其是在没有扩增的情况下。此外，研究队列中所有肿瘤内异质性高（定义为肿瘤区域或同时获取的样本之间基因组畸变差异达50%或更多）的患者在48个月后均存活。这些结果明确支持分析至少两个实体肿瘤区域（单独或混合）和液体样本，以便在HR-NB中提供更准确的基因组诊断、预后评估和治疗方案。
