Nancy Gillis 🆖☮️
@nancygillis.bsky.social
Molecular Epi | PGx | Hematology | @MoffittNews | Ad Lib Mom | Cancer Hater | Dog Lover | Explorer | PharmD @UFPharmacy | PhD @UNCPharmacy | *Opinions mine
Co-led with the always awesome @mingxiangteng.bsky.social with data from the #ORIENNetwork #AsterInsights and @moffittnews.bsky.social. #clonalhematopoiesis #CHIPsm
September 17, 2025 at 4:34 PM
Co-led with the always awesome @mingxiangteng.bsky.social with data from the #ORIENNetwork #AsterInsights and @moffittnews.bsky.social. #clonalhematopoiesis #CHIPsm
Thank you, again, to my incredibly collaborative team. This project has been such a joy. Can't wait to continue to build on this story!
September 3, 2025 at 11:51 AM
Thank you, again, to my incredibly collaborative team. This project has been such a joy. Can't wait to continue to build on this story!
These results provide compelling evidence for the clinical significance of changes in CH allelic abundance (VAFs) during cancer treatment with implications across solid tumor types. We shed light on genes and muts that may be more prone to positive selection.
September 3, 2025 at 11:51 AM
These results provide compelling evidence for the clinical significance of changes in CH allelic abundance (VAFs) during cancer treatment with implications across solid tumor types. We shed light on genes and muts that may be more prone to positive selection.
🚨 Finally, we show that, not CH in general, but **positive selection of CH muts** (eg, driven by chemo or radiation), is associated with OS, PFS, and RFS. These associations persist in multivariable, adjusted models.
September 3, 2025 at 11:51 AM
🚨 Finally, we show that, not CH in general, but **positive selection of CH muts** (eg, driven by chemo or radiation), is associated with OS, PFS, and RFS. These associations persist in multivariable, adjusted models.
These findings were corroborated in 2 external cohorts - one breast cancer and one pan-cancer cohort.
September 3, 2025 at 11:51 AM
These findings were corroborated in 2 external cohorts - one breast cancer and one pan-cancer cohort.
Neff was associated with dose - pts with higher exposure to chemo had smaller Neff (ie, stronger positive selection).
September 3, 2025 at 11:51 AM
Neff was associated with dose - pts with higher exposure to chemo had smaller Neff (ie, stronger positive selection).
We defined a fitness likelihood for each mut and calculated the probability of its clonal expansion relative to the wildtype alleles. The highest fitness likelihood was under tx with chemo, where the fittest CH muts per pt were over 10,000x more likely to expand than wildtype.
September 3, 2025 at 11:51 AM
We defined a fitness likelihood for each mut and calculated the probability of its clonal expansion relative to the wildtype alleles. The highest fitness likelihood was under tx with chemo, where the fittest CH muts per pt were over 10,000x more likely to expand than wildtype.
Neff: the min. # of clonally independent alleles needed to explain the observed changes in VAF during tx in a pt.
Low Neff: strong / positive selection;
High Neff: weak / negative or no selection.
Chemo and chemo+rad exerted the strongest selective pressure on CH clones.
Low Neff: strong / positive selection;
High Neff: weak / negative or no selection.
Chemo and chemo+rad exerted the strongest selective pressure on CH clones.
September 3, 2025 at 11:51 AM
Neff: the min. # of clonally independent alleles needed to explain the observed changes in VAF during tx in a pt.
Low Neff: strong / positive selection;
High Neff: weak / negative or no selection.
Chemo and chemo+rad exerted the strongest selective pressure on CH clones.
Low Neff: strong / positive selection;
High Neff: weak / negative or no selection.
Chemo and chemo+rad exerted the strongest selective pressure on CH clones.
We adapted a method for estimating pathogen transmission population size to calculate the number of alleles that recapitulated the observed mutational dynamics during tx per pt - the effective allelic population size (Neff).
September 3, 2025 at 11:51 AM
We adapted a method for estimating pathogen transmission population size to calculate the number of alleles that recapitulated the observed mutational dynamics during tx per pt - the effective allelic population size (Neff).
Long-term (up to 10 yr), CH VAFs continued to grow, with the largest increases in patients tx-ed with cytotoxic chemo.
September 3, 2025 at 11:51 AM
Long-term (up to 10 yr), CH VAFs continued to grow, with the largest increases in patients tx-ed with cytotoxic chemo.
The fitness landscape of CH is gene and mutation dependent. With chemo, TP53, YLPM1, PPM1D, and DNMT3A had the largest short-term changes in VAF. With breast radiation, ATM had the largest change in VAF. No effective changes in hormone tx only.
September 3, 2025 at 11:51 AM
The fitness landscape of CH is gene and mutation dependent. With chemo, TP53, YLPM1, PPM1D, and DNMT3A had the largest short-term changes in VAF. With breast radiation, ATM had the largest change in VAF. No effective changes in hormone tx only.
All post-tx CH muts were present before tx. All CHIP muts persisted at CHIP-defining VAFs; 4% of CH expanded to CHIP. Short-term, VAF changes were highest in pts tx-ed with chemo, followed by rad & chemo+rad; pts tx-ed with only hormone therapy had essentially no change in VAFs.
September 3, 2025 at 11:51 AM
All post-tx CH muts were present before tx. All CHIP muts persisted at CHIP-defining VAFs; 4% of CH expanded to CHIP. Short-term, VAF changes were highest in pts tx-ed with chemo, followed by rad & chemo+rad; pts tx-ed with only hormone therapy had essentially no change in VAFs.
55% of patients had #CH before tx; 33% had #CHIP. Of those with CH, 56% had only 1 mutation (mut). We quantified clonal diversity using divergence in variant allele frequencies (VAFs) and show that as CH expands, a larger number of CH muts may arise, increasing clonal diversity.
September 3, 2025 at 11:51 AM
We conducted ultra-deep error-corrected sequencing (>5000x) on serial samples from before, during, after, and long after treatment (tx) for breast cancer - with chemo, radiation, chemo+rad, or hormone therapy only - to measure CH changes over time.
September 3, 2025 at 11:51 AM
We conducted ultra-deep error-corrected sequencing (>5000x) on serial samples from before, during, after, and long after treatment (tx) for breast cancer - with chemo, radiation, chemo+rad, or hormone therapy only - to measure CH changes over time.
#ClonalHematopoiesis / #CHIP is associated with worse survival in pts treated for solid cancers, but the evolutionary mechanisms driving differential CH dynamics are unknown. To get at this, we calculated therapeutic bottleneck sizes in pts treated for cancer.
September 3, 2025 at 11:51 AM
#ClonalHematopoiesis / #CHIP is associated with worse survival in pts treated for solid cancers, but the evolutionary mechanisms driving differential CH dynamics are unknown. To get at this, we calculated therapeutic bottleneck sizes in pts treated for cancer.
📢 This has been a dream collaborative effort with an amazing group of investigators, notably @hkhiabanian.bsky.social, #MonaArabzadeh, #ShridarGanesan, #JeffreyWest, #SadeghMarzban, #StefaniaMorganti, @mingxiangteng.bsky.social, @jkresovich.bsky.social, @moffittnews.bsky.social, #NCI (funding)
September 3, 2025 at 11:51 AM
📢 This has been a dream collaborative effort with an amazing group of investigators, notably @hkhiabanian.bsky.social, #MonaArabzadeh, #ShridarGanesan, #JeffreyWest, #SadeghMarzban, #StefaniaMorganti, @mingxiangteng.bsky.social, @jkresovich.bsky.social, @moffittnews.bsky.social, #NCI (funding)
Linking identified variants to tumor sequencing (n > 390k patients), we show that pathogenic CH (#CHIP) mutations are commonly detected across tumor types and associated with 𝘺𝘰𝘶𝘯𝘨𝘦𝘳 age in patients with solid tumors suggesting differential biology.
March 24, 2025 at 3:27 PM
Linking identified variants to tumor sequencing (n > 390k patients), we show that pathogenic CH (#CHIP) mutations are commonly detected across tumor types and associated with 𝘺𝘰𝘶𝘯𝘨𝘦𝘳 age in patients with solid tumors suggesting differential biology.
We identified differences in SM and CH rates and mutations across genetic ancestry groups. We provide a catalogue of identified variants.
March 24, 2025 at 3:27 PM
We identified differences in SM and CH rates and mutations across genetic ancestry groups. We provide a catalogue of identified variants.
We used allele-balance and age skewing to identify SM and CH mutations in population-level data.
March 24, 2025 at 3:27 PM
We used allele-balance and age skewing to identify SM and CH mutations in population-level data.