1165-Centromeric DNA in ALT Cancer Telomeres

The research investigates a unique genetic phenomenon in Alternative Lengthening of Telomeres (ALT) cancers, where centromeric DNA sequences are abnormally incorporated into telomeric regions. This structural rearrangement, observed in both laboratory cell lines and pediatric neuroblastoma tumors, appears to be triggered by the loss of the ATRX protein and significant DNA hypomethylation. By utilizing advanced long-read sequencing and imaging techniques, the authors identified specific CENP-A chromatin footprints that reside at these modified telomeres. These centromeric signatures are not merely accidental; they appear to be vital for maintaining chromosomal stability and supporting the continued growth of ALT-positive cancer cells. Functional experiments show that disrupting these centromeric proteins leads to telomere fragmentation and impaired DNA synthesis during mitosis. Ultimately, the study suggests that while these insertions result from erroneous recombination, they become an essential adaptation for cancer cell survival.

References:

• Bhargava R, Mahlke M A, Schmidt T T, et al. Centromeric footprints preserve telomere integrity in ALT cancers[J]. Nature, 2026: 1-9.