Rewriting Cancer Detection: Hi-C Technology Uncovers Gene Fusions Missed by Standard Methods

A groundbreaking study from NYU Langone Health, Children’s Hospital Colorado, and Scripps Clinic has demonstrated how Arima Genomics’ Hi-C technology can detect gene fusions and chromosomal rearrangements in formalin-fixed, paraffin-embedded (FFPE) solid tumor specimens that current standard methods often miss.

The Challenge: Missing Critical Cancer Drivers

Chromosomal structural variants (SVs) are found in 95% of tumor samples and serve as both diagnostic markers and therapeutic targets. However, traditional methods like FISH and RNA sequencing have significant limitations—FISH is low-throughput and biased toward known rearrangements, while RNA sequencing struggles with degraded FFPE samples and can only detect variants that produce fusion transcripts.

Hi-C Technology: A Game-Changing Solution

High-throughput chromosome conformation capture (Hi-C) technology represents a paradigm shift in structural variant detection. Unlike traditional methods, Hi-C is a DNA-based approach that preserves spatial genome organization, enabling detection of both coding and non-coding structural variants with unprecedented sensitivity.

The Arima-HiC+ FFPE kit specifically addresses clinical sample challenges, generating comprehensive insights from archival tissues that correlate highly with fresh-frozen samples.

Impressive Clinical Results

The study analyzed 71 FFPE specimens from 10 different solid tumor types, revealing remarkable performance:

• 98% concordance with clinical FISH and RNA NGS for known variants
• 71% detection rate for structural variants in cases where previous methods failed
• 14% clinically actionable results among newly detected variants
• Additional 14% involved therapeutically targetable genes

Real-World Impact: Critical Diagnoses Unlocked

Case 1: A young patient with seizures initially thought to have a non-tumorous brain abnormality. While DNA methylation analysis and two RNA sequencing panels were inconclusive, Hi-C detected a MYBL1::MAML2 fusion, confirming low-grade glioma and enabling proper treatment.

Case 2: In a pediatric glioblastoma case, Hi-C detected a complex PD-L1 rearrangement missed by standard tests. Confirmatory testing revealed PD-L1 overexpression, opening immunotherapy opportunities.

How Hi-C Makes the Difference

Arima’s Hi-C technology maps the 3D genome architecture within FFPE samples, detecting structural variants with 100-1000 times higher signal than standard methods. The Arima-SV bioinformatics pipeline provides an end-to-end solution for identifying complex genomic rearrangements, including chromothripsis and extrachromosomal DNA.

The Future of Precision Oncology

This research builds on growing clinical evidence from collaborations with Yale, Harvard Medical School, and Seattle Children’s Hospital. As precision oncology evolves, comprehensive genome-wide structural variant analysis becomes essential for ensuring patients receive optimal treatments.

Hi-C technology’s integration into clinical workflows promises to unlock new diagnostic and therapeutic possibilities, representing a meaningful step toward more personalized cancer care by detecting actionable mutations that would otherwise remain hidden.

Click here to read the full story.