Table 1.

Additional biologic information through analysis of genetic heterogeneity

Technique	Spatial heterogeneity within the primary tumor or within metastases	Temporal heterogeneity during cancer progression
SNP-array, CGH, LOH-microsatellite analysis	Lower detection threshold for structural chromosomal aberrations and tumor suppressor gene deletions In the primary tumor: identification and differentiation of subclone lineages and of parallel evolution In metastases: identification of conserved genes	Lower detection threshold for structural chromosomal aberrations and tumor suppressor gene deletions Identification and differentiation of subclone lineages Identification of positive and negative selective pressure for the presence or loss of genes and pathways Identification of adaption mechanisms of the cancer genome under treatment
Gene specific Sanger-sequencing	Lower detection threshold for identification of driving mutations in the primary tumor: identification of subclones and of parallel evolution	Lower detection threshold for identification of driving mutations Identification of subclones Identification of positive selective pressure for gene mutations Identification of adaptive mutations under treatment
NGS on pooled cells	Lower detection threshold for identification of driving mutations Lower detection threshold for structural chromosomal aberrations and tumor suppressor gene deletions In the primary tumor: identification and differentiation of subclone lineages In metastases: identification of conserved genes and pathways	In addition: identification of adaptive mutations under treatment
NGS on single cells	Highest detection sensitivity for driving mutations, tumor suppressor gene deletions and structural chromosomal aberrations Identification and differentiation of subclone lineages Identification of conserved genes and pathways	In addition: lower detection threshold for identification of driving mutations Identification of adaptive mutations under treatment
Sanger sequencing or NGS of liquid biopsy	–	Identification and differentiation of subclone lineages Identification of adaptive mutations under treatment