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SUMMARY:Oncogene-like addiction to aneuploidy in human cancers - Jason She
 ltzer\, Yale School of Medicine
DTSTART:20230327T130000Z
DTEND:20230327T140000Z
UID:TALK194650@talks.cam.ac.uk
CONTACT:Estelle Heather Pepper
DESCRIPTION:Most cancers exhibit aneuploidy\, but its functional significa
 nce in tumor development is controversial. We have developed ReDACT (Resto
 ring Disomy in Aneuploid cells using CRISPR Targeting)\, a set of chromoso
 me 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 chro
 mosome 1q is required for malignant growth in cancers harboring this alter
 ation. Mechanistically\, gaining chromosome 1q increases the expression of
  MDM4 and suppresses TP53 signaling\, and we show that TP53 mutations are 
 mutually-exclusive with 1q aneuploidy in human cancers. Thus\, specific an
 euploidies play essential roles in tumorigenesis\, raising the possibility
  that targeting these “aneuploidy addictions” could represent a novel 
 approach for cancer treatment.
LOCATION:CRUK CI Lecture Theatre
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