Proud of this @NatureMedicine collaboration with #FeedmanLab on a novel method detecting early stage RCC in plasma&urine w/cell-free DNA methylomes. Work led by super stars @PierVitaleNuzzo @Jberchuck @keegankorthauer #SandorSpisak 
1/ RCC kills 175,000 patients worldwide with no screening test available acsjournals.onlinelibrary.wiley.com/doi/full/10.33….
A screening test that detects RCC while still localized (2/3 RCCs) will possibly reduce mortality. RCC and CNS tumors do not shed much cfDNA in the blood!
A screening test that detects RCC while still localized (2/3 RCCs) will possibly reduce mortality. RCC and CNS tumors do not shed much cfDNA in the blood!
2/ Developed initially by @decarvalho_lab (co-senior author), we validated this ultra-sensitive cfMeDIP-seq using plasma cfDNA and, for the 1st time, cfDNA from urine samples collected in our #GelbCenter (Chair M. Pomerantz)
3/ cfDNA methylation of classification of RCC and control samples based on plasma cfDNA methylation showed AUROC 0.99.
4/ No difference in RCC methylation score based on stage or histology.
5/ Being GU Oncologists (Yay!), and having access to bladder cancer samples, we partitioned RCC vs. UC. Again -->highly accurate classification: AUROC 0.979.
6/ What about URINE cfDNA methylation? Partitioning of RCC v. controls remained clear with AUROC 0.858.
7/ Few weeks ago, we compared for the 1st time cfDNA vs. methylated variants in metastatic RCC and showed much higher sensitivity for cfmethDNA (100% vs 21%). nature.com/articles/s4143… @jberchuck @PierVitaleNuzzo @AminNassarMD @sarahaboualaiwi with #Freedman/#kwiatkowski
8/ in Conclusion:
cfMeDIP-seq for RCC:
oHighly sensitive in plasma and urine
oDetects localized RCC
oDiscriminates between tumor types
cfMeDIP-seq for RCC:
oHighly sensitive in plasma and urine
oDetects localized RCC
oDiscriminates between tumor types
8/continued:
Many potential applications:
oEarly detection, benign kidney masses, high-risk population (targeted screening), guiding adjuvant therapy (MRD state), predicting response to therapy (mixed responses on imaging), early detection of AEs (since tissue-specific)?
Many potential applications:
oEarly detection, benign kidney masses, high-risk population (targeted screening), guiding adjuvant therapy (MRD state), predicting response to therapy (mixed responses on imaging), early detection of AEs (since tissue-specific)?
9/ I want to acknowledge our close collaborators: Steve Chang @BWHUrology @SLChang1, @rafalab @dfcidatasciences, Dror Michaelson @MassGeneralNews @AminNassarMD @sarahaboualaiwi @BrighamChiefs @roxs88 @ZiadBakouny @steinharterjack @CR_Curran @sonpavde and others!
10/ Early celebration from these 2 stars! Jake and Pier...but I don't see masks and I hope they are practicing social distancing! #COVID19 --well they working hard from home and have not missed a beat!
11/Please tune in to collaborator @decarvalho_lab on parallel paper in #GBM. Daniel is now talking @AACR virtual conference!-- Thank you for outstanding help from @NatureMedicine Associate Editor @SaheliSadanand!
cc: @kidneycan @KidneyCancer @IKCCorg @DanaFarberNews @CDMRP
cc: @kidneycan @KidneyCancer @IKCCorg @DanaFarberNews @CDMRP
