Convergent evolutionary trajectories uncover metastatic drivers in renal cancer
B
A
E
1. Loss of 9p drives metastatic disease in RCC
C
D
F
G
H
I
J
2. Metastatic RCC are characterized by high CIN and engagement of the cGAS/STING pathway
Leading Edge of Cancer Research Symposium, Houston, November 17 th –18 th , 2022 Luigi Perelli, MD, PhD - Genovese Lab, Genitourinary Medical Oncology
B
C
A
3. Transcriptomic single cell RNA seq & genomic data shows that RCC with loss of 9p mainly differ for the loss of 16q-
syntenic to human chromosome 21q
D
F
E
4. Loss of 21q drives down-modulation of the interferon pathway
K
J
G
I
H
B
C
A
5. Gain of function experiments using a model of Down Syndrome with partial trisomy of chromosome 21 is able to rescue the pro-tumorigenic phenotype induced by 21q loss 6. 21q loss pro- tumorigenic phenotype is driven by suppression of the interferon signaling
D
E
F
G
Conclusions: our findings indicate that metastatic dissemination of clear-cell and non-clear-cell RCC is driven by CIN, following a model of punctuated equilibrium. We also discovered a tumor suppressive role of chromosome 21q. These findings elucidate molecular drivers of metastatic dissemination in RCC and may provide new biomarkers to intercept and prevent aggressive clinical behavior.
Page 1 Page 2 Page 3Made with FlippingBook interactive PDF creator