Publications by authors named "A Rowan"
Using joint genomic-transcriptomic analysis of 243 samples, we reveal recurrent patterns of nongenetic evolution in ccRCC not exclusively governed by genetic factors, including T-cell depletion, tumor T-cell receptor coevolution, potential cGAS-STING repression, and increased cell proliferation. These patterns can aid clinical management and guide novel treatment approaches.
View Article and Find Full Text PDFWhile the key aspects of genetic evolution and their clinical implications in clear cell renal-cell carcinoma (ccRCC) are well-documented, how genetic features co-evolve with the phenotype and tumor microenvironment (TME) remains elusive. Here, through joint genomic-transcriptomic analysis of 243 samples from 79 patients recruited to the TRACERx Renal study, we identify pervasive non-genetic intratumor heterogeneity, with over 40% not attributable to genetic alterations. By integrating tumor transcriptomes and phylogenetic structures, we observe convergent evolution to specific phenotypic traits, including cell proliferation, metabolic reprogramming and overexpression of putative cGAS-STING repressors amid high aneuploidy.
View Article and Find Full Text PDFHuman T-cell leukaemia virus type-1 (HTLV-1) causes the highly aggressive malignancy adult T-cell leukaemia-lymphoma (ATL) in approximately 5 % of chronically infected carriers. HTLV-1 persists in the host by enhancing survival of infected-T-cells despite the presence of a strong immune response. Therefore, asymptomatic HTLV-1 carriers have a lifelong balance between infected cell proliferation and the host antiviral immune response.
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- - The study introduces the SPRINTER algorithm, which analyzes single-cell DNA sequencing to identify and classify the proliferation rates of different cancer cell clones within tumors, shedding light on the variability of cell growth among these clones.
- - Applying SPRINTER to nearly 15,000 non-small cell lung cancer cells showed significant differences in clone proliferation, which was corroborated by various imaging techniques and indicated that more proliferative clones also had a higher likelihood of metastasis and altered genetic replication patterns.
- - The algorithm's effectiveness was further demonstrated in breast and ovarian cancer datasets, where it uncovered higher proliferation rates and genetic variations in specific, more rapidly growing cell clones.
Extrachromosomal DNA (ecDNA) is a major contributor to treatment resistance and poor outcome for patients with cancer. Here we examine the diversity of ecDNA elements across cancer, revealing the associated tissue, genetic and mutational contexts. By analysing data from 14,778 patients with 39 tumour types from the 100,000 Genomes Project, we demonstrate that 17.
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