Deep analysis! Genomic blueprint features for advanced cancer!

May 27, 2020 /
PRNewswire
BIOON/ -- Scientists from Massachusetts General Hospital have revealed a genome blueprint for advanced cancer in a recent review published in the international
journal nature cancerentitled "The Landscape of Advanced Cancer." Although scientists have made great strides in cancer therapy research in recent years, cancer metastasis and therapeutic resistance remain the leading causes of cancer-related death worldwide, and in this review, researchers map the comprehensive molecular map of advanced cancer and post-treatmenttumor, as well as combining genome-wide and transcriptome analysis with clinical prognosis in cancer patientsPicture Source: Rheinbay, ENat Cancer, doi: 10.1038/s43018-020-0057-z
primary tumors tend to carry differentgeneticdrive changes that promote cancer cells to bypass the host body's cellular control mechanisms and grow, and over the past 10 years, thousands of primary tumors have been exposed to exoplasmosis The group and whole genome sequencing provide researchers with detailed maps of the drivers of mutations in multiple types of cancer, however, the researchers have not delved into the
geneticchanges that inducetumor
recurrence and the spread of cancer to other organs, and in this paper, researcher Marra et alstudied 570 patients with advanced or metastatic cancer, analyzing information such as whole genome sequencing data, transcriptocycial group characteristics, and the prognosis of therapy the molecular characteristics of metastatic tumors face unique challenges, and although primary malignancies are usually surgically removed, and researchers can easily identify specimens, they are not usually clinically removed due to difficulty in removing and the risks to patients; Sampleing metastatic tumors requires a fine needle biopsy, which requires careful evaluation of the risks and benefits; for example, this method captures only a small number of cells at the tumor site, limiting tumor cloning that can be sampled and limiting researchers' understanding of the structure and microenvironment of tumors in addition, the unique history of individual therapeutic exposure (which can vary greatly in type and treatment time) can increase heterogeneity between individual samples, even for the same type of patient, which can have very complex effects on genomic events, therapies, and patient prognosis To address these issues, the researchers studied body samples from 570 patients recruited to the POG570 (Personalized Oncogenomics program of the British Columbia Personalized Oncology Genomics Program), which covered 25 histology, including some rare types of cancer, who received multiple cancer drugs Treatment, including endocrine therapy, chemotherapy, and immuno-checkpoint inhibitor therapy, has previously been done primarily using genomic or exobiome sequencing, which can be used as an excellent tool for identifying specific genetic mutations, compared with current work to sequence the entire tumor genomes, and locate the authors' study of non-coding mutations, structural mutations, and mutation characteristics genome-wide analysis provides researchers with the opportunity to help identify genetic -driven mutations in cancer in each patient and to help study such mutations in tumor queues, a prominent issue in the current field of research is that researchers are not sure whether the metastatic spread of cancer or therapeutic tolerance is caused by changes that affect specific gene or genomic regions Consistent with previous studies, the blueprints for drive mutations in this cohort study largely reflect the correlation between histology-like primary tumor , and although the researchers did not find universal genetic drivers in metastatic specific genes, they found specific drug resistance mutations in targeted genes for specific treatments In principle, future researchers are still likely to find some advanced drivers in less researched non-coding areas and larger tumor groups, and Marra and his simultaneous research support the hypothesis that metastatic processes may be largely driven by changes in epigenetic
Compared to the lack of driven mutations, the researchers identified significant differences in mutations in late-stage and metastatic tumors and primary tumor , and whole genome sequencing can help researchers obtain a large number of mutations compared to limited signals from gene detection boxes and exogenous group sequencing, which can help to identify the mutation semalic characteristics that drive cancer, which may also serve as mutases that have been or continueto exposed by cells, such as tobacco smoke, ultraviolet light, and endogenous APOC When the researchers analyzed the body mutation characteristics of participants in the POG570 queue, they observed characteristics similar to primary cancer, and they also revealed several signatures of the therapeutic-related characteristic mutations, and found that the number of characteristic mutations increased significantly as long-term exposure to platinum drugs, tamoxifen, or radiotherapy Picture Source: Rheinbay, E Nat Cancer, doi: 10.1038/s43018-020-0057-z
The researchers also observed that the overall number of mutations in tumors was associated with the time the patient was exposed to genotoxic ity sedatives, mutation burdens and genomic scars The increase may be the expected consequence of DNA damage treatment, but this effect is particularly pronounced when tumor carry mutations in the error-prone polymerase or POLQ gene, which is an important component of the DNA damage repair pathway The researchers also say mutagenic therapy also gives cancer cells the opportunity to accumulate new mutations in cancer genes to gain selective adaptation advantages, and later researchers need to conduct more in-depth research in this area to identify and prevent the emergence of new drivers induced by thetherapy using matching genomics and transcriptomics techniques, the researchers further analyzed eight different groups of immune phenotypes, which are largely independent of the histology and metastasis of the tumor, but are directly related to tumor survival; Research aimed at describing late-stage and post-treatment tumors may face some common challenges, starting with the difficulty of obtaining primary tumor specimens from patients with advanced or metastatic diseases who have entered clinical trials , and without matching original samples, it is not possible for researchers to directly compare pre- and post-treatment genetic and transcriptomics characteristics, as well as the trajectory of disease transmission in individual patients Second, late-stage tumors tend to have inherent heterogeneity, especially after the use of different drugs or treatments, which complicates the
identification of genomic changes and characteristics associated with specific disease regimens and treatments; based on previous research, later researchers will continue to study advanced cancers, and genomic scientists must continue to work to increase the representation of other ancestors in similar projects to ensure that all cancer patients
benefit; (biovalleybioon.com) References: Rheinbay, E.
The genomic landscape of the .
Nat Cancer
1, 372-373 (2020) doi:10.1038/s43018-020-0057-z