Current Application Status and Future Trends of Genome Sequencing in the Field of Tumors

Advantages and Disadvantages of Genome Sequencing for Tumor Diagnosis

Genome sequencing has a wide range of applications, including the detection of non-coding regions, large-scale structural variations, viral genomes, mitochondrial genetic changes, immune genomes, and more. However, in some cases, the shallow read depth of genome sequencing can lead to false-negative results, especially in cases with high intratumoral heterogeneity. Additionally, the need for frozen tumor tissue, high costs for data analysis and storage, and challenges in identifying unknown genetic abnormalities are factors limiting its clinical applications.

Research Progress in Genome Sequencing for Tumor Diagnosis

The Pan-Cancer Analysis of Whole Genomes (PCAWG) is initiated by the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), providing the most comprehensive cancer genome meta-analysis to date. Key findings include: ① Cancer genomes on average contain 4-5 driver gene mutations, but no driver gene mutations are found in about 5% of cases. ② Chromothripsis is an early event in tumor evolution. ③ Tumors with high-frequency telomere misregulation mechanisms mainly originate from tissues with low replication activity. ④ A few non-coding region mutations that cause cancer have been discovered.

In another study on "somatic non-coding mutations" conducted by the PCAWG consortium, researchers developed a mutation identification method integrating 13 algorithms. They discovered point mutations in the 5’ region of TP53, point mutations in the 3' untranslated region of NFKBIZ and TOB1, and rearrangements in BRD4 and AKR1C genes. For structural variations, two new methods were introduced to identify regions with significant recurrent breakpoints and significant recurrent juxtaposition.

Clinical Applications of Genome Sequencing for Tumor Diagnosis

United Kingdom: 100,000 Genomes Project

Launched in 2012, the project includes around 85,000 NHS patients affected by rare disease or cancer. As part of this project, genome sequencing is provided as a routine medical service. At the same time, the project is also expanding collaboration with different organizations and the industry, marking a significant milestone.

Netherlands: Clinical Practice of Genome Sequencing

A unique aspect of the Netherlands is that since 2021, genome sequencing for diagnosing cancers of unknown primary origin has become a reimbursable item under health insurance. Dutch researchers have developed an algorithm that can accurately predict the primary site of cancers of unknown primary origin based on genome sequencing results. In a study comparing genome sequencing with standard molecular diagnostics for care among 848 patients, 190 (22.4%) received additional treatment based on the genome sequencing results. Moreover, the world's largest metastatic tumor genome sequencing database, the Hartwig Medical Foundation Database, is also located in the Netherlands.

Future Trends in Genome Sequencing for Tumor Diagnosis

Genome sequencing has become a transformative tool in the field of cancer genomics and will further aid in personalized diagnosis and treatment, identification of rare mutations, and elucidation of tumor evolution and heterogeneity. Meanwhile, challenges related to data sharing, ethics, and high-quality healthcare continue to exist. International collaboration is crucial in overcoming these challenges, and through collective efforts, genome sequencing will demonstrate greater value in the fight against tumors.