Publications
Our research has been published in leading scientific journals, advancing the field of cancer genomics and precision medicine.
Liquid versus tissue biopsy for detecting acquired resistance and tumor heterogeneity in gastrointestinal cancers
Parikh, Aparna R.*, Ignaty Leshchiner*, Liudmila Elagina, Lipika Goyal, Chaya Levovitz, Giulia Siravegna, Dimitri Livitz et al.
Here, in a prospective cohort of 42 patients with molecularly defined gastrointestinal cancers and acquired resistance to targeted therapy, direct comparison of postprogression cfDNA versus tumor biopsy revealed that cfDNA more frequently identified clinically relevant resistance alterations and multiple resistance mechanisms, detecting resistance alterations not found in the matched tumor biopsy in 78% of cases.
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Growth dynamics in naturally progressing chronic lymphocytic leukaemia
Gruber, Michaela*, Ivana Bozic*, Ignaty Leshchiner*, Dimitri Livitz*, Kristen Stevenson, Laura Rassenti, Daniel Rosebrock et al.
Each growth pattern was associated with marked differences in genetic composition, the pace of disease progression and the extent of clonal evolution. ... we found that dynamic changes in the disease course of CLL were shaped by the genetic events that were already present in the early slow-growing stages. Finally, by analysing the growth rates of subclones compared with their parental clones, we quantified the growth advantage conferred by putative CLL drivers in vivo.
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The Evolutionary History of 2,658 Cancers
Gerstung, Moritz*, Clemency Jolly*, Ignaty Leshchiner*, Stefan C. Dentro*, Santiago Gonzalez*, Daniel Rosebrock, Thomas J. Mitchell, ... , Dimitri Livitz et al.
Our study sheds light on the typical timescales of in vivo tumour development, with initial driver events seemingly occurring up to decades before diagnosis, demonstrating how cancer genomes are shaped by a lifelong process of somatic evolution, with fluid boundaries between normal ageing processes and cancer evolution.
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Characterizing genetic intra-tumor heterogeneity across 2,658 human cancer genomes
Dentro, Stefan C., Ignaty Leshchiner, Kerstin Haase, Maxime Tarabichi, Jeff Wintersinger, Amit G. Deshwar, Kaixian Yu, ... , Dimitri Livitz et al.
We observe positive selection of subclonal driver mutations across most cancer types and identify cancer type-specific subclonal patterns of driver gene mutations, fusions, structural variants, and copy number alterations as well as dynamic changes in mutational processes between subclonal expansions.
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Evolutionary History of Transformation from Chronic Lymphocytic Leukemia to Richter Syndrome
Parry, Erin M.*, Ignaty Leshchiner*, Romain Guièze*, Connor Johnson, ... , Dimitri Livitz et al.
We distinguished pathways that were dysregulated in RS versus CLL, and detected clonal evolution of transformation at single-cell resolution, identifying intermediate cell states. Our study defines distinct molecular subtypes of RS and highlights cell-free DNA analysis as a potential tool for early diagnosis and monitoring.
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Inferring Early Genetic Progression in Cancers with Unobtainable Premalignant Disease
Leshchiner, Ignaty*, Edmund A. Mroz*, Justin Cha*, Daniel Rosebrock, Oliver Spiro, Juliana Bonilla-Velez, William C. Faquin, et al.
Our approach can establish previously unknown early genetic progression of cancers with unobtainable premalignant tissue, supporting development of experimental models and methods for early detection, interception and prognostication.
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