CircRNAs Are Here to Stay: A Perspective on the Recombinome.

Chromosomal translocations harbored by cancer genomes are important oncogenic drivers. In rearranged acute leukemia (MLLre) fuses with over 90 partner genes. Mechanistic studies provided clues of MLL fusion protein leukemogenic potential, but models failed to fully recapitulate the disease. Recently, expression of oncogenic fusion circular RNAs (f-circ) by fusion was proven. This discovery, together with emerging data on the importance and diversity of circRNAs formed the incentive to study the circRNAs of the recombinome. Through interactions with other RNAs, such as microRNAs, and with proteins, circRNAs regulate cellular processes also related to cancer development. CircRNAs can translate into functional peptides too. and most of the 90 translocation partners do express circRNAs and exploration of our RNA-seq dataset of sorted blood cell populations provided new data on alternative circular isoform generation and expression variability of circRNAs of the recombinome. Further, we provided evidence that rearrangements of and three of the main translocation partner genes can impact circRNA expression, supported also by preliminary observations in leukemic cells. The emerging picture underpins the view that circRNAs are worthwhile to be considered when studying MLLre leukemias and provides a new perspective on the impact of chromosomal translocations in cancer cells at large.