Ignaty Leshchiner
Chief, Computational Oncology and Biostatistics, Yale Cancer CenterCards
About
Research
Publications
2026
Actionable genetic landscape and dynamics in circulating DNA from 12,827 patients with metastatic breast cancer
Leshchiner I, Medford AJ, Cha J, Kiedrowski LA, Niemierko A, Keenan JC, Dai CS, Spring LM, Moy B, Wander SA, Vidula N, Isakoff SJ, Juric D, Miller M, Davis AA, Gerratana L, Shah A, Park BH, Brufsky A, O’Shaughnessy J, Nagy RJ, Ellisen LW, Cristofanilli M, Bardia A, Getz G. Actionable genetic landscape and dynamics in circulating DNA from 12,827 patients with metastatic breast cancer. Nature Communications 2026 DOI: 10.1038/s41467-026-75976-9.Peer-Reviewed Original ResearchThis study shows that liquid biopsy—blood-based tumor DNA testing—reveals widespread treatment-resistance mutations across 12,827 patients with metastatic breast cancer.Complex structural variations functionally inactivate the telomerase chaperone TCAB1 in osteosarcoma
Keegan J, Sorbello S, Mori J, Muratani S, Leshchiner I, Heaphy C, Flynn R. Complex structural variations functionally inactivate the telomerase chaperone TCAB1 in osteosarcoma. BMC Cancer 2026, 26: 948. PMID: 42243724, PMCID: PMC13455141, DOI: 10.1186/s12885-026-16250-5.Peer-Reviewed Original Research
2025
Tamoxifen induces PI3K activation in uterine cancer
Kübler K, Nardone A, Anand S, Gurevich D, Gao J, Droog M, Hermida-Prado F, Akhshi T, Feiglin A, Feit A, Cohen Feit G, Dackus G, Pun M, Kuang Y, Cha J, Miller M, Gregoricchio S, Lanfermeijer M, Cornelissen S, Gibson W, Paweletz C, Van Allen E, van Leeuwen F, Nederlof P, Nguyen Q, Mourits M, Radovich M, Leshchiner I, Stewart C, Matulonis U, Zwart W, Maruvka Y, Getz G, Jeselsohn R. Tamoxifen induces PI3K activation in uterine cancer. Nature Genetics 2025, 57: 2192-2202. PMID: 40846762, PMCID: PMC12425819, DOI: 10.1038/s41588-025-02308-w.Peer-Reviewed Original ResearchA neoantigen vaccine generates antitumour immunity in renal cell carcinoma
Braun D, Moranzoni G, Chea V, McGregor B, Blass E, Tu C, Vanasse A, Forman C, Forman J, Afeyan A, Schindler N, Liu Y, Li S, Southard J, Chang S, Hirsch M, LeBoeuf N, Olive O, Mehndiratta A, Greenslade H, Shetty K, Klaeger S, Sarkizova S, Pedersen C, Mossanen M, Carulli I, Tarren A, Duke-Cohan J, Howard A, Iorgulescu J, Shim B, Simon J, Signoretti S, Aster J, Elagina L, Carr S, Leshchiner I, Getz G, Gabriel S, Hacohen N, Olsen L, Oliveira G, Neuberg D, Livak K, Shukla S, Fritsch E, Wu C, Keskin D, Ott P, Choueiri T. A neoantigen vaccine generates antitumour immunity in renal cell carcinoma. Nature 2025, 639: 474-482. PMID: 39910301, PMCID: PMC11903305, DOI: 10.1038/s41586-024-08507-5.Peer-Reviewed Original ResearchAdultAgedAntigens, NeoplasmCancer VaccinesCarcinoma, Renal CellClass I Phosphatidylinositol 3-KinasesDNA-Binding ProteinsFemaleHumansIpilimumabKidney NeoplasmsMaleMiddle AgedMutationPrecision MedicineT-LymphocytesTranscription FactorsTumor Suppressor ProteinsUbiquitin ThiolesteraseVon Hippel-Lindau Tumor Suppressor Protein
2024
A model for decoding resistance in precision oncology: acquired resistance to FGFR inhibitors in cholangiocarcinoma
Goyal L, DiToro D, Facchinetti F, Martin E, Peng P, Baiev I, Iyer R, Maurer J, Reyes S, Zhang K, Majeed U, Berchuck J, Chen C, Walmsley C, Pinto C, Vasseur D, Gordan J, Mody K, Borad M, Karasic T, Damjanov N, Danysh B, Wehrenberg-Klee E, Kambadakone A, Saha S, Hoffman I, Nelson K, Iyer S, Qiang X, Sun C, Wang H, Li L, Javle M, Lin B, Harris W, Zhu A, Cleary J, Flaherty K, Harris T, Shroff R, Leshchiner I, Parida L, Kelley R, Fan J, Stone J, Uboha N, Hirai H, Sootome H, Wu F, Bensen D, Hollebecque A, Friboulet L, Lennerz J, Getz G, Juric D. A model for decoding resistance in precision oncology: acquired resistance to FGFR inhibitors in cholangiocarcinoma. Annals Of Oncology 2024, 36: 426-443. PMID: 39706336, DOI: 10.1016/j.annonc.2024.12.011.Peer-Reviewed Original ResearchDevelopmental mosaicism underlying EGFR-mutant lung cancer presenting with multiple primary tumors
Burr R, Leshchiner I, Costantino C, Blohmer M, Sundaresan T, Cha J, Seeger K, Guay S, Danysh B, Gore I, Jacobs R, Slowik K, Utro F, Rhrissorrakrai K, Levovitz C, Barth J, Dubash T, Chirn B, Parida L, Sequist L, Lennerz J, Mino-Kenudson M, Maheswaran S, Naxerova K, Getz G, Haber D. Developmental mosaicism underlying EGFR-mutant lung cancer presenting with multiple primary tumors. Nature Cancer 2024, 5: 1681-1696. PMID: 39406916, PMCID: PMC11584400, DOI: 10.1038/s43018-024-00840-y.Peer-Reviewed Original ResearchTracking Rare Single Donor and Recipient Immune and Leukemia Cells after Allogeneic Hematopoietic Cell Transplantation Using Mitochondrial DNA Mutations.
Penter L, Cieri N, Maurer K, Kwok M, Lyu H, Lu W, Oliveira G, Gohil S, Leshchiner I, Lareau C, Ludwig L, Neuberg D, Kim H, Li S, Bullinger L, Ritz J, Getz G, Garcia J, Soiffer R, Livak K, Wu C. Tracking Rare Single Donor and Recipient Immune and Leukemia Cells after Allogeneic Hematopoietic Cell Transplantation Using Mitochondrial DNA Mutations. Blood Cancer Discovery 2024, 5: 442-459. PMID: 39236287, PMCID: PMC11528187, DOI: 10.1158/2643-3230.bcd-23-0138.Peer-Reviewed Original ResearchCrowd-sourced benchmarking of single-sample tumor subclonal reconstruction
Salcedo A, Tarabichi M, Buchanan A, Espiritu S, Zhang H, Zhu K, Ou Yang T, Leshchiner I, Anastassiou D, Guan Y, Jang G, Mootor M, Haase K, Deshwar A, Zou W, Umar I, Dentro S, Wintersinger J, Chiotti K, Demeulemeester J, Jolly C, Sycza L, Ko M, Wedge D, Morris Q, Ellrott K, Van Loo P, Boutros P. Crowd-sourced benchmarking of single-sample tumor subclonal reconstruction. Nature Biotechnology 2024, 43: 581-592. PMID: 38862616, PMCID: PMC11994449, DOI: 10.1038/s41587-024-02250-y.Peer-Reviewed Original Research
2023
Allosteric PI3K-alpha inhibition overcomes on-target resistance to orthosteric inhibitors mediated by secondary PIK3CA mutations.
Varkaris A, de la Cruz F, Martin E, Norden B, Chevalier N, Kehlmann A, Leshchiner I, Barnes H, Ehnstrom S, Stavridi A, Yuan X, Kim J, Ellis H, Papatheodoridi A, Gunaydin H, Danysh B, Parida L, Sanidas I, Ji Y, Lau K, Wulf G, Bardia A, Spring L, Isakoff S, Lennerz J, Del Vecchio K, Pierce L, Pazolli E, Getz G, Corcoran R, Juric D. Allosteric PI3K-alpha inhibition overcomes on-target resistance to orthosteric inhibitors mediated by secondary PIK3CA mutations. Cancer Discovery 2023, 14: 227-239. PMID: 37916958, PMCID: PMC10850944, DOI: 10.1158/2159-8290.cd-23-0704.Peer-Reviewed Original ResearchGenetic events associated with venetoclax resistance in CLL identified by whole-exome sequencing of patient samples
Khalsa J, Cha J, Utro F, Naeem A, Murali I, Kuang Y, Vasquez K, Li L, Tyekucheva S, Fernandes S, Veronese L, Guieze R, Sasi B, Wang Z, Machado J, Bai H, Alasfour M, Rhrissorrakrai K, Levovitz C, Danysh B, Slowik K, Jacobs R, Davids M, Paweletz C, Leshchiner I, Parida L, Getz G, Brown J. Genetic events associated with venetoclax resistance in CLL identified by whole-exome sequencing of patient samples. Blood 2023, 142: 421-433. PMID: 37146250, PMCID: PMC10447490, DOI: 10.1182/blood.2022016600.Peer-Reviewed Original Research