Long-hidden 'junk DNA' regions may help explain cancer-linked genome instability
· Medical Xpressedited by Lisa Lock, reviewed by Andrew Zinin
Lisa Lock
Scientific Editor
Meet our editorial team
Behind our editorial process
Andrew Zinin
Lead Editor
Meet our editorial team
Behind our editorial process Editors' notes
This article has been reviewed according to Science X's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility:
fact-checked
peer-reviewed publication
trusted source
proofread
The GIST Add as preferred source
Many repetitive regions of the genome have been considered "junk DNA" because the available technologies did not allow them to be studied at sufficient resolution. This is the case for the SST1/NBL2 macrosatellites, considered irrelevant and, until now, virtually invisible, which may have a more complex and decisive biological role than previously thought in nuclear organization, genome regulation, chromosomal instability and even cancer.
This is the conclusion of an article published in the journal Trends in Genetics, led by researchers Sonia V. Forcales, from the Faculty of Medicine and Health Sciences at the University of Barcelona and the Bellvitge Biomedical Research Institute, and Gabrijela Dumbović, from Goethe University Frankfurt in Germany.
The study, published in the forum section of the journal, gathers evidence accumulated over years along with the most recent advances in structural genomics on these largely unknown components of the human genome. Because SST1/NBL2 are primate-specific sequences, the study may also help answer evolutionary questions about the biological function of repetitive DNA in humans and other primates.
Repetitive and altered regions in human tumors
The SST1/NBL2 satellites have been associated with cancer, particularly through epigenetic and transcriptional alterations. They are located mainly on acrocentric chromosomes (with unequal arms) and are a highly valuable model "because they concentrate many of the extreme characteristics of the human repetitive genome: they are large tandemly repeated sequences, with high structural complexity, dynamic epigenetic regulation and the production of noncoding RNAs," says Forcales, from the Department of Pathology and Experimental Therapeutics at the UB and principal investigator of the Immunity, Inflammation and Cancer research group at IDIBELL.
In cancer, these repetitive regions of the genome are frequently demethylated—the loss of methyl CH3 groups—one of the most common epigenetic alterations in human tumors. The team contributed to characterizing the epigenetic dysregulation in these macrosatellites and to describing TNBL, a noncoding RNA derived from NBL2 regions frequently hypomethylated in tumors. This transcript can interact with factors involved in splicing, the DNA damage response and nucleolar function.
"This suggests possible connections between the repetitive genome and functional molecular processes in tumor biology. However, we still do not know to what extent SST1/NBL2 are directly involved in these processes or what the exact underlying mechanism is," the researcher notes.
Recent studies have also identified the regions containing SST1/NBL2 as genomic loci involved in Robertsonian translocations, the most common chromosomal rearrangements in humans. When these rearrangements involve chromosome 21, they can give rise to a form of trisomy 21 that accounts for a minority of Down syndrome cases.
"These data do not indicate that SST1/NBL2 is the sole cause, but they do reinforce the idea that these regions may contribute to the structural vulnerability of acrocentric chromosomes. In this context, these macrosatellites are relevant because they are located in acrocentric regions involved in this type of rearrangement, but it cannot be concluded that they are the direct cause of the pathology," the researcher notes.
Other human diseases have also been linked to families of macrosatellites and repetitive genome sequences. For example, the D4Z4 macrosatellite is involved in facioscapulohumeral muscular dystrophy, and alterations in the methylation of repetitive regions such as SST1/NBL2 and D4Z4 have been described in ICF syndrome, a rare disease associated with immunodeficiency, chromosomal instability and facial anomalies.
A revolution in the study of the human repetitive genome
Current techniques allow researchers to study regions of the genome considered irrelevant not because they were, but because the necessary tools to explore their biological complexity did not exist. "The great challenge is no longer to fully sequence the human genome, but to understand the function of the repetitive regions that for decades lay outside the focus of genomics," says Forcales.
Long-read sequencing technologies—such as Oxford Nanopore and PacBio—and the new telomere-to-telomere, or T2T, assemblies of the human genome have revolutionized the ability to reconstruct regions such as SST1/NBL2, which consist of large arrays of similar repeated sequences and had, until recently, been absent, fragmented or poorly represented in reference genomes produced by more conventional technologies.
In parallel, traditional techniques—RNA-FISH, DNA-FISH, RNA pull-down and Northern blot—have been key to studying their nuclear localization, the expression of the RNAs derived from these sequences and their molecular interactions.
This new level of resolution is already transforming the way the human repetitive genome can be studied.
For example, "it will make it possible to study variability between individuals, between tumors, as well as their epigenetic marks and SST1/NBL2-derived RNAs more reliably," the authors point out.
In the future, the team aims to characterize possible variants or isoforms of these RNAs, as well as their regulation and epigenetic modifications. The goal is to determine whether these RNAs play a functional role in tumor processes, rather than being merely a consequence of cancer-related epigenetic dysregulation.
"We are still in a basic research phase, but if we confirm that these RNAs functionally contribute to tumor processes, it could open up new avenues to explore their role as biomarkers or therapeutic vulnerabilities," the researcher concludes.
Publication details
Gabrijela Dumbović et al, The structure and regulatory biology of the SST1/NBL2 macrosatellite family, Trends in Genetics (2026). DOI: 10.1016/j.tig.2026.03.004
Journal information: Trends in Genetics
Clinical categories
OncologyClinical genetics Provided by University of Barcelona Who's behind this story?
Lisa Lock
BA art history, MA material culture. Former museum editor, paramedic, and transplant coordinator. Editing for Science X since 2021. Full profile →
Andrew Zinin
Master's in physics with research experience. Long-time science news enthusiast. Plays key role in Science X's editorial success. Full profile →
Citation: Long-hidden 'junk DNA' regions may help explain cancer-linked genome instability (2026, June 5) retrieved 5 June 2026 from https://medicalxpress.com/news/2026-06-hidden-junk-dna-regions-cancer.html This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.