Single-cell diploid Hi-C reveals the role of spatial aggregations in complex rearrangements and KMT2A fusions in leukemia.

ABSTRACT:

Background

Simple translocations and complex rearrangements are formed through illegitimate ligations of double-strand breaks of fusion partners and lead to generation of oncogenic fusion genes that affect cellular function. The contact first hypothesis states that fusion partners tend to colocalize prior to fusion in normal cells. Here we test this hypothesis at the single-cell level and explore the underlying mechanism.

Results

By analyzing published single-cell diploid Hi-C datasets, we find partner genes fused in leukemia exhibit smaller spatial distances than those fused in solid tumor and control gene pairs. Intriguingly, multiple partners tend to colocalize with KMT2A in the same cell. 3D genome architecture has little association with lineage decision of KMT2A fusion

SUBMITTER: Xing Z 

PROVIDER: S-EPMC9361544 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature