Assessing Hi-C Sequencing for Gene Fusion Detection in Pediatric Tumors

Chobeilin Yan^*
*Correspondence: Chobeilin Yan, Department of Pediatrics, National Sun Yat-Sen University, Kaohsiung 80424, Taiwan, Email:

Introduction

The detection of gene fusions is crucial in the diagnosis and treatment of various cancers, including both hematologic and solid tumors. Gene fusions, which result from chromosomal rearrangements, can create novel oncogenic drivers and influence tumor behavior, response to therapy and prognosis. Traditionally, methods such as Fluorescence In Situ Hybridization (FISH) and Reverse Transcription Polymerase Chain Reaction (RT-PCR) have been employed to identify specific gene fusions. However, these techniques can be limited by their need for prior knowledge of the fusion partners and may not capture the full spectrum of potential fusions. Hi-C sequencing, a powerful genome-wide chromatin interaction capture technique, offers a novel approach to identifying gene fusions by providing a comprehensive view of the three-dimensional structure of the genome. By revealing interactions between different genomic regions, Hi-C sequencing can potentially uncover previously undetected gene fusions and chromosomal abnormalities. Evaluating the efficacy of Hi-C sequencing in detecting gene fusions, particularly in pediatric cancer samples, could significantly advance our understanding of cancer genomics and improve diagnostic accuracy [1].

Description

Hi-C sequencing works by cross-linking and capturing interactions between distant chromosomal regions, followed by high-throughput sequencing to map these interactions. This method generates a detailed contact map of the genome, highlighting regions that interact with one another, which can be indicative of chromosomal rearrangements and gene fusions. Unlike targeted approaches, Hi-C sequencing does not require prior knowledge of fusion partners, making it a versatile tool for discovering novel fusions that may be missed by conventional methods. In pediatric cancers, where gene fusions often play a critical role in tumorigenesis and can serve as biomarkers for diagnosis and therapeutic targeting, the ability to identify a broad range of fusions is particularly valuable. Hi-C sequencing has the potential to enhance the detection of gene fusions in both hematologic malignancies, such as leukemia and lymphoma and solid tumors, including neuroblastoma and sarcomas. By applying Hi-C sequencing to pediatric cancer samples, researchers aim to evaluate its effectiveness in uncovering fusion genes, comparing its performance with existing diagnostic methods and assessing its utility in clinical practice [2].

Hi-C sequencing's comprehensive approach allows for the simultaneous detection of multiple gene fusions and chromosomal abnormalities within a single experiment. This method generates high-resolution interaction maps of the entire genome, revealing structural variations and spatial genome organization that may lead to the formation of novel fusion genes. In pediatric cancers, where the tumor genome often harbors unique and diverse fusions, Hi-C sequencing provides a valuable tool for uncovering previously unknown genetic alterations that could be pivotal for diagnosis and treatment. The workflow of Hi-C sequencing involves several key steps: first, chromatin from the cancer cells is cross-linked to preserve the three-dimensional structure of the genome. Next, the DNA is fragmented and interacting fragments are ligated together to form chimeric molecules. These chimeric molecules are then sequenced and the resulting data are used to create a contact map that highlights regions of the genome that interact frequently. By analyzing these interaction maps, researchers can identify regions where gene fusions are likely to occur based on their proximity and interactions [3].

One of the strengths of Hi-C sequencing is its ability to detect both recurrent and rare gene fusions across a broad spectrum of cancers. For hematologic malignancies, where specific gene fusions are known to be characteristic of certain subtypes (e.g., BCR-ABL1 in chronic myeloid leukemia), Hi-C sequencing can provide a more comprehensive view of potential additional fusions that might contribute to disease progression or drug resistance. Similarly, in solid tumors such as neuroblastoma or Ewing sarcoma, where gene fusions often drive oncogenesis, Hi-C sequencing can uncover novel fusion events that may be critical for understanding tumor biology and developing targeted therapies. Furthermore, Hi-C sequencing holds promise for identifying genetic alterations that may not be captured by targeted assays due to their limited scope [4]. For instance, while FISH and RT-PCR are excellent for detecting known fusions, they are less effective at identifying novel or unexpected fusions. Hi-C sequencing’s genomewide approach can overcome this limitation, offering insights into the full spectrum of genetic rearrangements present in pediatric cancer samples. In addition to its diagnostic potential, Hi-C sequencing may also contribute to the discovery of new therapeutic targets and biomarkers. By identifying novel gene fusions and understanding their role in tumor biology, researchers can develop targeted treatments aimed at specific fusion proteins or the pathways they influence. This could lead to more effective and personalized treatment options for pediatric cancer patients, ultimately improving clinical outcomes. Overall, Hi-C sequencing represents a significant advancement in cancer genomics, with the potential to transform our approach to diagnosing and treating pediatric cancers by providing a more complete and nuanced understanding of the genetic landscape of these diseases [5].

Conclusion

In conclusion, evaluating Hi-C sequencing for gene fusion detection represents a promising advancement in cancer genomics, with significant implications for the diagnosis and treatment of pediatric cancers. The comprehensive nature of Hi-C sequencing offers the potential to identify a wide range of gene fusions, including those not detectable by traditional methods. This capability could enhance diagnostic accuracy, uncover novel oncogenic drivers and inform personalized treatment strategies for pediatric patients. As research progresses, it will be essential to validate Hi-C sequencing's effectiveness in diverse clinical settings and compare its results with established diagnostic techniques. Successful integration of Hi-C sequencing into routine clinical practice could lead to improved outcomes by providing a more complete picture of genomic alterations in pediatric cancers, ultimately contributing to better-targeted therapies and more precise management of these complex diseases.

Acknowledgement

None.

Conflict of Interest

None.

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