The role of exon sequencing in tumor molecular typing (II)

The role of exon sequencing in tumor molecular typing.

The existence of tumor heterogeneity makes it almost difficult to find exactly the same tumor cells in the same tumor body of the same tumor patient. Accurate typing of tumors will more clearly define the clinical stage of the tumor, provide guidance for treatment and prognosis judgment. There is a large difference between the sensitivity of different molecular types of the same tumor to chemotherapeutic drugs. For tumor patients with poor sensitivity to chemotherapeutic drugs, other options such as immunotherapy or targeted therapy can be selected. Molecular typing of drug reactivity is significant. In the application of tumor molecular typing, exon sequencing technology can not only provide information on the types of gene mutations and gene copy number changes, but also find relevant signal pathways, cell differentiation levels, transcriptional changes, proteins, epigenetics and other information. On the other hand, while studying nucleotide changes and chromosome structural mutations in tumor primary tumors, exon sequencing can also study metastatic tumor and xenograft DNA. This information has become a favorable basis for tumor molecular typing. This has provided a reliable basis for tumor molecular typing based on exon sequencing.

In the molecular typing of primary tumors, exon sequencing data combined with clinical applications can not only improve the accuracy of molecular typing of tumors but also improve diagnostic efficiency. Using such high-throughput sequencing technology, researchers can find many genes related to primary tumors and reveal their characteristics during tumorigenesis and development, and then accurately type tumors.

In the molecular typing of metastatic tumors, due to the interaction of the microenvironment of the anatomical site and other factors, there may be differences in molecular subtypes between the metastatic tumor and the primary tumor. Combined with research methods such as exon sequencing, the assessment of patients with invasive bladder cancer consistency between molecular subtypes, biomarkers and lymph node metastases, only a small part of the bladder tumors and lymph node metastases were inconsistent in the experimental results. Most of the inconsistent cases were basal / squamous subtype bladder cancer, and it is suggested that when studying basal / squamous subtype bladder cancer and its related drug targets (such as EGFR, MET, STAT 3), the heterogeneity of bladder tumors and the inconsistency of molecular subtypes in metastatic tumors should be considered simultaneously.

In the molecular typing of tumors associated with microlesions, microlesions in vivo refer to short DNA sequences of variable repeats. These DNA fragments are prone to mutations such as insertions and deletions. It is difficult to find these tiny DNA fragments with the naked eye. These microlesions and tumors relationship is not very clear. In order to detect these small DNA sequences more efficiently, combined with exon sequencing, more than 1,000 previously unreported tumor-related microlesions have been found, and the in vivo role of microlesions in the body has been confirmed. The number and changes such as insertion and deletion can distinguish between micro-lesion stable tumors and micro-lesion unstable tumors. Therefore, it is possible to improve clinically relevant subtypes of tumors.

Exon sequencing is reliable for tumor molecular typing. In the past, tumor-generating organs were used as the basis, and sub-classifications were determined based on patient age, cell type, and tissue classification. Exon sequencing technology provides tumor DNA, RNA, and protein mutation data for tumor molecular typing. The result is that the marker-dependent detection can be used to determine the molecular typing of tumors, and the results are very reliable. In order to apply next-generation sequencing technologies such as exon sequencing from academic research to clinical diagnosis and judge prognosis, it has also triggered many international discussions on the clinical application of next-generation sequencing technologies, and promoted a series of next-generation sequencing technologies in clinical practice. The use of guidelines and regulations was produced, covering all aspects of ethics, patient education, data processing, and clinical reporting, which gave strict reference standards for the clinical application of exon sequencing. In the context of clinical oncology, the transition of sub-sequencing from clinical research to clinical application will greatly help cancer treatment in individual patients. Exon sequencing is applied to tumor molecular typing to achieve "same disease and different treatment" and "different disease and same treatment". At present, the understanding of tumor subgroups is far from enough. On the basis of exon sequencing, we know the molecular typing of tumors. We can choose different treatment options based on different molecular types of the same tumor, or tumors with different pathological characteristics. The same molecular basis can choose the same treatment. Exon sequencing can detect changes in gene copy number. Different tumors may be classified into the same subtype due to the same copy number. Therefore, the same treatment scheme can be used to classify tumors from different tissues into "a class" to achieve "different diseases with the same treatment." These molecular classifications have changed the concept of traditional medicine and made it possible to treat the same disease and treat different diseases in the future. Exon sequencing confirms tumor molecular typing to reduce tissue dependence. Exon sequencing technology was used to detect and compare the circulating tumor DNA (ctDNA) in the plasma of 18 tumor patients with 46 genes between the tumor metastasis tissues. As a result, the gene mutations found in 97% of tissues were detected in plasma. Gene mutations found in a few plasma samples were also detected, but were not found in the tissues, suggesting that exon sequencing can detect plasma ctDNA instead of detecting tissue DNA in tumor genotyping and individualized treatment.

The development of exon sequencing technology has made it possible to conduct more accurate research on tumors at the molecular level, and increased identification of potential driver mutations in tumors. Exon sequencing provides new clues to clarify the pathogenesis of tumors, and has broad prospects in tumor molecular typing, so that individualized and precise treatments based on tumor molecular typing can be realized.

References

[1] Crystel Bonnet, M'hamed Grati, Sandrine Marlin. Complete exon sequencing of all known Usher syndrome genes greatly improves molecular diagnosis[J]. Orphanet Journal of Rare Diseases, 2011, 6(1):21.

[2] Jiantao Wu, Krzysztof R Grzeda, Chip Stewart. Copy Number Variation detection from 1000 Genomes Project exon capture sequencing data[J]. Bmc Bioinformatics, 2012, 13(1):305.

[3] Miyagawa Maiko, Naito Takehiko. Targeted Exon Sequencing Successfully Discovers Rare Causative Genes and Clarifies the Molecular Epidemiology of Japanese Deafness Patients[J]. Plos One, 8(8):e71381-.