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The History of the Philadelphia Chromosome: How to Reveal the Truth About Genetic Recombination in Cancer Research?
In the field of cancer research, the discovery of the Philadelphia chromosome is undoubtedly a disruptive milestone. The discovery of this small abnormal chromosome marked the beginning of an important link between genetic recombination and cancer, and opened up a new horizon for modern oncology.
Oncogenes and fusion genes
A fusion gene is a hybrid gene composed of two independent genes. It is usually formed due to chromosomal translocation, internal deletion or chromosomal inversion.
As early as the 1980s, scientists first described fusion genes in cancer cells. The basis of this research originated from the discovery of small abnormal marker chromosomes in patients with chronic myelogenous leukemia in Philadelphia in 1960 by Peter Nowell and David Hungerford. This result also Make the Philadelphia Chromosome an important symbol of cancer research. In 1973, Janet Rowley revolutionized our understanding of chromosomal abnormalities by discovering that this chromosome was formed via a translocation between chromosomes 9 and 22. Subsequently, the researchers further confirmed that this translocation led to the formation of a new BCR::ABL1 fusion gene, which is considered an oncogene and can cause chronic myelogenous leukemia.
Catalysts for tumor formation
Statistics show that the formation of many tumors is closely related to fusion genes. These fusion genes often produce abnormal proteins that are more active than non-fusion genes, which is the source of their cancer-causing properties. For example, fusion genes such as BCR-ABL and TMPRSS2-ERG are important factors that promote cancer progression. Among them, TMPRSS2-ERG regulates prostate cancer development by disrupting androgen receptor (AR) signaling. Most fusion genes are mainly found in blood cancers, sarcomas, and prostate cancers. There is also a fusion gene called BCAM-AKT2, which is specifically associated with high-grade plasma cell ovarian cancer.
Applications in diagnosis
Specific chromosomal abnormalities and their corresponding fusion genes are widely used in cancer diagnosis to help doctors target accurate diagnoses.
Currently, detection methods such as chromosomal banding analysis, in situ hybridization (FISH), and reverse transcription polymerase chain reaction (RT-PCR) are widely used in clinical laboratories. However, these methods still have limitations in the face of the complexity of cancer genomes. In recent years, the development of high-throughput sequencing and customized DNA microarrays has provided the possibility for more efficient diagnostic methods.
The evolution and new discoveries of gene fusion
The importance of gene fusion in the evolution of genetic structure cannot be underestimated. It not only promotes the emergence of new genes, but also affects the expression regulation of genes. Gene fusion in coding regions can lead to the formation of new genes and thus new functions. When this event occurs in non-coding regions, it may lead to misregulation of gene expression. With the advancement of technology, researchers have now detected many gene fusion events across the genome, which will help to gain a deeper understanding of the multi-module architecture of proteins.
Future research and applications
With advances in next-generation sequencing technology, scientists are able to screen known and novel gene fusion events genome-wide. The Transcriptome Viewer (TViewer) developed by the researchers is a visualization tool that can help visually observe the detected fusion genes. These technologies not only provide a deeper understanding of gene fusion, but also provide new ways for early diagnosis and targeted treatment of cancer.
Fusion genes are not only important tools in cancer research, they also have broad application potential in gene expression research. Scientists can deliberately create fusion genes that combine regulatory elements of specific reporter genes with target genes to help reveal the regulatory mechanisms of genes and even better understand the mechanisms of disease in humans and other organisms. As our understanding of fusion genes deepens, can we find more effective treatment strategies to combat cancers caused by genetic recombination in the future?
