echemi logo
Product
  • Product
  • Supplier
  • Inquiry
    Home > Biochemistry News > Biotechnology News > "Science" How many steps does it take to accurately transform normal cells into cancer cells?

    "Science" How many steps does it take to accurately transform normal cells into cancer cells?

    • Last Update: 2022-05-09
    • Source: Internet
    • Author: User
    Search more information of high quality chemicals, good prices and reliable suppliers, visit www.echemi.com

    Scientists have identified thousands of cancer gene mutations over the past 20 years, but understanding how these genetic mutations affect tumor growth and spread in the body remains a challenge because each patient's tumor may have many different genes mutation


    This has led to the inference of genotype and phenotype linkages in cancer patients, and being able to systematically link genetic mutations or combinations of mutations in cancer with their phenotypes will greatly advance our understanding of cancer pathogenesis and help develop corresponding Treatment and medication


    29 April 2022, Aviv Regev et al


    The research team used CRISPR-Cas9 gene editing technology to sequentially edit five melanoma-related gene mutations or a combination in healthy human skin melanocytes


    These edited cells grew and proliferated into tumors with melanoma characteristics, including rapid growth, enhanced invasiveness, and specific patterns of gene activation and pigmentation


    Because the study can introduce one mutation at a time, the specific effects of specific genetic mutations and combinations of mutations can be determined


    The study's lead author, Eran Hodis, is a doctoral student in the lab of Aviv Regev, now at Harvard's Brigham and Women's Hospital.


    According to Eran Hodis, the study is the first to use precisely controlled genetic engineering techniques to create a human cancer model from fully differentiated cells rather than stem cells


    This approach will provide the opportunity to create similar models in many other cancers, helping to accelerate the study of the association of cancer genetics with specific disease characteristics


    To design these cancer models, precise gene editing techniques must be combined with high-resolution, massively parallel single-cell genomics analysis to generate and characterize cells and tumors, and to analyze the data through machine learning


    Taken together, these findings give us an unprecedented understanding of which genetic mutations and combinations cause cells to become cancerous


    When studying melanoma, linking its genotype to a specific trait or phenotype is especially difficult


    Therefore, there are many genetic mutations in melanoma patients that are caused by external factors, and most of these genetic mutations are not drivers of melanoma


    By introducing the gene mutation into healthy human melanocytes, the effect of the gene mutation on melanoma can be observed without interference


    The research team first used CRISPR-Cas9 gene editing to sequentially introduce mutations in the genes CDKN2A, BRAF and TERT, which are normally found in melanomas in healthy human melanocytes


    Next, the research team knocked out the known melanoma-related tumor suppressor genes PTEN, TP53, and APC in the above-mentioned cells to generate a total of nine different cell models:

    • Wild-type human melanocytes (WT),

    • CDKN2A-/- cells (C),

    • CDKN2A-/-+BRAF V600E cells (CB),

    • CDKN2A-/-+BRAF V600E+TERT-124C>T cells (CBT),

    •CDKN2A-/-+BRAF V600E+TERT-124C>T+TP53-/- cells (CBT3),

    •CDKN2A-/-+BRAF V600E+TERT-124C>T+PTEN-/- cells (CBTP),

    • CDKN2A-/-+BRAF V600E+TERT-124C>T+APC-/- cells (CBTA),

    •CDKN2A-/-+BRAF V600E+TERT-124C>T+PTEN-/-+TP53-/- cells (CBTP3),

    •CDKN2A-/-+BRAF V600E+TERT-124C>T+PTEN-/-+APC-/- cells (CBTPA)


    The research team implanted the above nine cell models into mice and observed them
    .

    Single-cell RNA sequencing revealed that these cells gradually altered their gene expression programs as more genetic mutations were introduced, and that mouse tumor models had similar gene expression patterns and pigmentation patterns to human melanoma patients with the same genotype
    .

    This suggests that the de novo melanoma cells faithfully mirror tumors in human melanoma patients
    .

    A striking feature of melanoma is the onset of metastasis at an early stage of the cancer, and this study clearly shows that CBTA cells and CBTPA cells are the most metastatic cells, that is, APC knockout cells are the most metastatic cells type, suggesting that inactivation of our APC gene may contribute to melanoma metastasis
    .

    The study also showed that CDKN2A-/-+BRAF V600E+TERT-124C>T mutations, when together, caused cells to behave like cancer cells and divide indefinitely
    .

    Tumors grew fastest when the above three mutations were combined with inactivation of the PTEN and TP53 genes
    .


    Overall, this study used CRISPR-Cas9 gene editing technology to edit human healthy melanocytes, gradually introducing 1 to 5 gene mutations, involving 6 gene mutations commonly found in melanoma, namely CDKN2A, BRAF, TERT, PTEN, TP53 , APC
    .
    A total of 9 cell models with different genes were constructed
    .

    These models were then characterized in vitro and in vivo using physiological assessments, histopathology, single-cell RNA sequencing, and machine learning algorithms
    .

    Through these cellular models, melanocyte genotypes correlate with phenotypes such as gene expression programs, replication and immortality, malignancy, rapid growth, pigmentation patterns, tumor metastasis, and histopathological features
    .
    and identified genetic mutations responsible for melanoma growth, metastasis and changes in the tumor microenvironment
    .

    In addition, this study not only revealed key genetic mutations in melanoma, but also provided a new way to study the role of specific genes in cancer
    .

    This article is an English version of an article which is originally in the Chinese language on echemi.com and is provided for information purposes only. This website makes no representation or warranty of any kind, either expressed or implied, as to the accuracy, completeness ownership or reliability of the article or any translations thereof. If you have any concerns or complaints relating to the article, please send an email, providing a detailed description of the concern or complaint, to service@echemi.com. A staff member will contact you within 5 working days. Once verified, infringing content will be removed immediately.

    Contact Us

    The source of this page with content of products and services is from Internet, which doesn't represent ECHEMI's opinion. If you have any queries, please write to service@echemi.com. It will be replied within 5 days.

    Moreover, if you find any instances of plagiarism from the page, please send email to service@echemi.com with relevant evidence.