Oncogene-like addiction to aneuploidy in human cancers.

Autor:	Girish V; Yale University School of Medicine, New Haven, CT 06511, USA.; Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA., Lakhani AA; Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA., Thompson SL; Yale University School of Medicine, New Haven, CT 06511, USA., Scaduto CM; Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA., Brown LM; Yale University School of Medicine, New Haven, CT 06511, USA., Hagenson RA; Yale University School of Medicine, New Haven, CT 06511, USA., Sausville EL; Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA., Mendelson BE; Yale University School of Medicine, New Haven, CT 06511, USA., Kandikuppa PK; Yale University School of Medicine, New Haven, CT 06511, USA., Lukow DA; Yale University School of Medicine, New Haven, CT 06511, USA., Yuan ML; Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA., Stevens EC; Yale University School of Medicine, New Haven, CT 06511, USA., Lee SN; Yale University School of Medicine, New Haven, CT 06511, USA., Schukken KM; Yale University School of Medicine, New Haven, CT 06511, USA., Akalu SM; Yale University School of Medicine, New Haven, CT 06511, USA., Vasudevan A; Yale University School of Medicine, New Haven, CT 06511, USA., Zou C; Yale University School of Medicine, New Haven, CT 06511, USA., Salovska B; Yale University School of Medicine, New Haven, CT 06511, USA., Li W; Yale University School of Medicine, New Haven, CT 06511, USA., Smith JC; Yale University School of Medicine, New Haven, CT 06511, USA., Taylor AM; Columbia University School of Medicine, New York, NY 10032, USA., Martienssen RA; Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.; Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA., Liu Y; Yale University School of Medicine, New Haven, CT 06511, USA., Sun R; Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA., Sheltzer JM; Yale University School of Medicine, New Haven, CT 06511, USA.
Jazyk:	angličtina
Zdroj:	Science (New York, N.Y.) [Science] 2023 Aug 25; Vol. 381 (6660), pp. eadg4521. Date of Electronic Publication: 2023 Aug 25.
DOI:	10.1126/science.adg4521
Abstrakt:	Most cancers exhibit aneuploidy, but its functional significance in tumor development is controversial. Here, we describe ReDACT (Restoring Disomy in Aneuploid cells using CRISPR Targeting), a set of chromosome engineering tools that allow us to eliminate specific aneuploidies from cancer genomes. Using ReDACT, we created a panel of isogenic cells that have or lack common aneuploidies, and we demonstrate that trisomy of chromosome 1q is required for malignant growth in cancers harboring this alteration. Mechanistically, gaining chromosome 1q increases the expression of MDM4 and suppresses p53 signaling, and we show that TP53 mutations are mutually exclusive with 1q aneuploidy in human cancers. Thus, tumor cells can be dependent on specific aneuploidies, raising the possibility that these "aneuploidy addictions" could be targeted as a therapeutic strategy.
Databáze:	MEDLINE
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