Cell free DNA and Cell tumor DNA
Non cell bound DNA fragments are shed into circulation as cell free DNA (cfDNA). Circulating tumor DNA (ctDNA) which is cfDNA from tumor cells is shed into blood through apoptosis, necrosis or through an active process from neoplastic cells. Molecular aberrations in tumor tissues such as point mutations, insertions, deletions and methylation profiles are present in these circulating DNA fragments (55,56,57,58,59). The fragmentation pattern of ctDNA in healthy people has been found to be different from the pattern in patients with various kinds of cancers (60). Surveillance circulating tumor DNA identifies patients at risk of recurrence in DLBCL with a positive predictive value of 88.2% and negative predictive value of 97ยท8% (61). Unlike CTCs and exosomes which contain RNA and proteins together with DNA, ctDNA provides no proteomic and transcriptomic information.
Immunoglobulin gene rearrangement is another novel technology for identifying prognostic groups in DLBC. Molecular characterization of immunoglobulin gene rearrangements revealed distinct subgroups in non-GCB (62). DLBCL patients with immunoglobulin gene rearrangement have been shown to have a lower rate of complete remission and significantly poorer survival. (63).