Rlf–Mycl Gene Fusion Drives Tumorigenesis and Metastasis in a Mouse Model of Small Cell Lung Cancer | Zendy

Metamia Ciampricotti | Zendy; Triantafyllia Karakousi | Zendy; Allison L. Richards | Zendy; Álvaro Quintanal-Villalonga | Zendy; Angeliki Karatza | Zendy; Rebecca Caeser | Zendy; Emily A. Costa | Zendy; Viola Allaj | Zendy; Parvathy Manoj | Zendy; Kyle B. Spainhower | Zendy; Faruk Erdem Kombak | Zendy; Francisco J. SánchezRivera | Zendy; Janneke E. Jaspers | Zendy; AnastasiaMaria Zavitsanou | Zendy; Danilo Maddalo | Zendy; Andrea Ventura | Zendy; William M. Rideout | Zendy; Elliot H. AkamaGarren | Zendy; Tyler Jacks | Zendy; Mark T.A. Donoghue | Zendy; Triparna Sen | Zendy; Trudy G. Oliver | Zendy; John T. Poirier | Zendy; Thales Papagiannakopoulos | Zendy; Charles M. Rudin | Zendy

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Rlf–Mycl Gene Fusion Drives Tumorigenesis and Metastasis in a Mouse Model of Small Cell Lung Cancer

Author(s) -

Metamia Ciampricotti,

Triantafyllia Karakousi,

Allison L. Richards,

Álvaro Quintanal-Villalonga,

Angeliki Karatza,

Rebecca Caeser,

Emily A. Costa,

Viola Allaj,

Parvathy Manoj,

Kyle B. Spainhower,

Faruk Erdem Kombak,

Francisco J. SánchezRivera,

Janneke E. Jaspers,

AnastasiaMaria Zavitsanou,

Danilo Maddalo,

Andrea Ventura,

William M. Rideout,

Elliot H. AkamaGarren,

Tyler Jacks,

Mark T.A. Donoghue,

Triparna Sen,

Trudy G. Oliver,

John T. Poirier,

Thales Papagiannakopoulos,

Charles M. Rudin

Publication year - 2021

Publication title -

cancer discovery

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 6.795

H-Index - 163

eISSN - 2159-8290

pISSN - 2159-8274

DOI - 10.1158/2159-8290.cd-21-0441

Subject(s) - carcinogenesis , fusion gene , cancer research , metastasis , biology , lung cancer , crispr , cancer , gene , computational biology , medicine , pathology , genetics

Small cell lung cancer (SCLC) has limited therapeutic options and an exceptionally poor prognosis. Understanding the oncogenic drivers of SCLC may help define novel therapeutic targets. Recurrent genomic rearrangements have been identified in SCLC, most notably an in-frame gene fusion between RLF and MYCL found in up to 7% of the predominant ASCL1-expressing subtype. To explore the role of this fusion in oncogenesis and tumor progression, we used CRISPR/Cas9 somatic editing to generate a Rlf-Mycl-driven mouse model of SCLC. RLF-MYCL fusion accelerated transformation and proliferation of murine SCLC and increased metastatic dissemination and the diversity of metastatic sites. Tumors from the RLF-MYCL genetically engineered mouse model displayed gene expression similarities with human RLF-MYCL SCLC. Together, our studies support RLF-MYCL as the first demonstrated fusion oncogenic driver in SCLC and provide a new preclinical mouse model for the study of this subtype of SCLC.

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