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        How moles change

        into melanoma

               oles and melanomas are                                            mutations. We might also be able to
               both skin tumors that come                                        combat melanoma by changing the
        Mfrom the same cell called                                               environment.”
        melanocytes. The difference is that
        moles are usually harmless, while                                        These findings create a foundation
        melanomas are cancerous and                                              for researching potential melanoma
        often deadly without treatment. In                                       biomarkers, allowing doctors to
        a study published today in eLife                                         detect cancerous changes in
        Magazine, Robert Judson-Torres,                                          the blood at earlier stages. The
        PhD, Huntsman Cancer Institute                                           researchers are also interested in
        (HCI) researcher and University of                                       using these data to better understand
        Utah (U of U) assistant professor                                        potential topical agents to reduce
        of dermatology and oncological                                           the risk of melanoma, delay
        sciences, explains how common                                            development, or stop recurrence, and
        moles and melanomas form and why                                         to detect melanoma early.
        moles can change into melanoma.
                                                                                 The study was funded by National
        Melanocytes are cells that give                                          Institutes of Health/National Cancer
        color to the skin to protect it from   profiling and digital holographic   Institute including P30 CA042014,
        the sun’s rays. Specific changes to   cytometry. Transcriptomic profiling   5 For The Fight, and Huntsman
        the DNA sequence of melanocytes,     lets researchers determine molecular   Cancer Foundation. Judson-Torres
        called BRAF gene mutations, are      differences between moles and       recognizes critical contributions by
        found in over 75% of moles. The      melanomas. Digital holographic      other HCI scientists, including Rachel
        same change is also found in 50%     cytometry helps researchers track   Belote, PhD; Sheri Holmen, PhD;
        of melanomas and is common in        changes in human cells.             Matthew VanBrocklin, PhD; David
        cancers like colon and lung. It was                                      Lum, PhD; Doug Grossman, MD,
        thought that when melanocytes only   “We discovered a new molecular      PhD; and University of California San
        have the BRAFV600E mutation          mechanism that explains how moles   Francisco scientists Andrew McNeal,
        the cell stops dividing, resulting in   form, how melanomas form, and    PhD; Maria Wei, MD, PhD; and
        a mole. When melanocytes have        why moles sometimes become          Ursula Lang, MD, PhD.
        other mutations with BRAFV600E,      melanomas,” says Judson-Torres.
        they divide uncontrollably, turning                                      Story Source:
        into melanoma. This model is called   The study shows melanocytes that   Materials provided by Huntsman
        “oncogene-induced senescence.”       turn into melanoma do not need to   Cancer Institute. Note: Content may
                                             have additional mutations but are   be edited for style and length.
        “A number of studies have            actually affected by environmental
        challenged this model in recent      signaling, when cells receive signals   Journal Reference:
        years,” says Judson-Torres. “These   from the environment in the skin    1. Andrew S McNeal, Rachel L
        studies have provided excellent      around them that give them direction.   Belote, Hanlin Zeng, Marcus Urquijo,
        data to suggest that the oncogene-   Melanocytes express genes in        Kendra Barker, Rodrigo Torres,
        induced senescence model does        different environments, telling them   Meghan Curtin, A Hunter Shain,
        not explain mole formation but what   to either divide uncontrollably or stop   Robert HI Andtbacka, Sheri Holmen,
        they have all lacked is an alternative   dividing altogether.            David H Lum, Timothy H McCalmont,
        explanation -- which has remained                                        Matt W VanBrocklin, Douglas
        elusive.”                            “Origins of melanoma being          Grossman, Maria L Wei, Ursula
                                             dependent on environmental          E Lang, Robert L Judson-Torres.
        With help from collaborators across   signals gives a new outlook in     BRAFV600E induces reversible
        HCI and the University of California   prevention and treatment,” says   mitotic arrest in human melanocytes
        San Francisco, the study team took   Judson-Torres. “It also plays a role   via microrna-mediated suppression
        moles and melanomas donated by       in trying to combat melanoma by     of AURKB. eLife, 2021; 10 DOI:
        patients and used transcriptomic     preventing and targeting genetic    10.7554/eLife.70385

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