Visualization of intra tumor heterogeneity by simultaneous analysis of tumor and liquid biopsy samples in stage M neuroblastomas

Introduction:

Intra-tumoral heterogeneity (ITH) is a major challenge for the detection of relevant genomic aberrations in primary tumor (TU) biopsies. Hence, there is an unmet need for alternative analytic procedures to obtain a more complete picture of the genomic landscape and to minimize sampling error in tumor patients. Analyzing cell-free tumor DNA (ctDNA) from more easily accessible patient biomaterial could surmount these challenges.

Method:

We compared the genomic results (SNP array or low coverage WGS) of different DNA sources: TU, disseminated tumor cells (DTCs) and/or ctDNA from peripheral blood (PB) and/or bone marrow (BM) plasma of 38 stage M neuroblastoma patients.

Results:

ctDNA derived from PB or BM allowed the identification of most gene aberrations present in the primary TU. However, we found a higher number of genomic aberrations in the PB-ctDNA as compared to the corresponding primary TUs. On top of this, the DTCs showed additional unique aberrations that were shared only with the ctDNA from the BM. Thus, the genomic make up of DTCs and ctDNA within the BM seems to be identical indicating an independent compartment.

Conclusion:

With these data, we will be able to better understand ITH and tumor progression and draw conclusions on the most informative type of DNA to address the most relevant clone for a possible relapse.