Computational modeling of locoregional recurrence with spatial structure identifies tissue-specific carcinogenic profiles

Abubakar, Sharafudeen Dahiru; Takaki, Mitsuaki; Haeno, Hiroshi

doi:10.3389/fonc.2023.1116210

Cited by 3 publications

(1 citation statement)

References 71 publications

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“…The Cancer Genome Atlas (TCGA) is a rich computational resource for the genomic and mutational data for different cancer types [9,10] and has been helpful in genomic studies [9,11], validation of biomarkers [12], and the design of computational oncology models [13]. This means that accuracy and robustness of the data are essential for research, modeling, and clinical usage.…”

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confidence: 99%

Exploring racial disparities in bladder urothelial cancer: insights into survival and genetic variations

Abubakar,

Bello,

Gusau

et al. 2024

Afr J Urol

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Background Bladder urothelial cancer is the most common malignancy of the urinary system and the 10th most common cancer worldwide with incidence appearing to show a geographical and exposure pattern. Advances in genomic technologies provide abundant data and insight into tumors at the single-cell resolution and are usually stored in repositories like The Cancer Genome Atlas (TCGA). However, data sources for the TCGA appear to be focused on European and American populations. The extent to which genomic and survival data can be applied to populations not included in the study remains somewhat uncertain. Methods We explored the genomic and survival characteristics of the TCGA pan-cancer atlas of bladder urothelial cancer. We decluttered these characteristics based on racial groups and compared between and among the races and the overall dataset. Results Significant variations were seen in age groups especially Asians (51–60) years and Blacks (61–70) years compared to Whites and the BLCA dataset with a statistically significant difference in mean diagnosis age (p = 0.0048) between Asians and the whole dataset. Overall survival characteristics were similar but genetic features were vastly different. Significant inter-racial alterations could be seen among genes involved in different pathways, oncogenes, tumor suppressors, cytoband amplification and/or deletion, mutation count, and aneuploidy scores. Conclusion The TCGA pan-cancer atlas for bladder urothelial cancer adequately represents White populations only. The genomic features do not apply to Blacks and Asians. We recommend better coverage for other populations to ensure adequate data for clinicians and researchers.

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confidence: 99%

Exploring racial disparities in bladder urothelial cancer: insights into survival and genetic variations

Abubakar,

Bello,

Gusau

et al. 2024

Afr J Urol

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Patient-specific computational models predict prognosis in B cell lymphoma by quantifying pro-proliferative and anti-apoptotic signatures from genetic sequencing data

Norris

Jones

Mancini

et al. 2023

Preprint

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Genetic heterogeneity and co-occurring driver mutations contribute to poor clinical outcomes in cancer. However, the impact of multiple mutations on complex signalling networks is not easily predicted. We found that, by placing mutations into their cellular context, multi-scale agent-based mathematical models could predict how genetic events combine in haematological malignancies. Simulations of lymphoma and myeloma predicted co-occurring mutations synergised to increase tumour cell expansion beyond what would be expected from the impact of the individual mutations alone. Mutational synergy between MYC and BCL2 was consistent with the more aggressive disease course of patients with double-hit lymphoma, and mutational synergy between MCL1 and CKS1B was predictive of outcome in patients with gain 1q multiple myeloma. Incorporating patient-specific mutational profiles into personalised models of lymphoma patients with the worst clinical outcomes revealed a correlation between simulated mutational synergy and overall survival, which outperformed widely used classifications of lymphoma informed by gene expression or mutational data alone. Our results demonstrated that mutational synergy scores enabled prediction of the impact of co-occurring mutations and may improve personalised prognostic predictions.

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Multistage carcinogenesis in occupational cholangiocarcinoma: the impact of clonal expansion and risk estimation

Watanabe,

Haeno,

Mimaki

et al. 2024

Genes and Environ

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Background Both mutation induction and clonal expansion of mutated cells cause cancer. The probability of cancer development depends on mutations, clonal growth rates, and carcinogenic mechanisms. A recent study showed cases of occupational cholangiocarcinomas that originate multifocally, with higher mutation burden levels than those in common cholangiocarcinomas. This study aimed to identify the effect of clonal expansion on and estimate the risk of occupational and common intrahepatic cholangiocarcinomas (ICCs) using a multistage model modified to include the effect of cell expansion at any carcinogenic stage. Methods The age-specific incidence of common ICC estimated from the Vital Statistics in Japan and the prognosis of ICC, and mutation frequencies of occupational and common ICC available from the previous report, were applied to a multistage model modified with cell proliferation effects. From the fittest model, the risk after exposure was estimated. Results The required number of stages for carcinogenesis was estimated to be three based on the incidences and mutation frequencies of occupational and common ICCs. Based on this estimation, the predicted incidence curve under the model was similar to that estimated from the ICC mortality rate, except for older adults. The model indicated a minor effect of clonal expansion on the observed occupational ICC risk. It predicted a rapid decrease in ICC risk after the cessation of occupational exposure, although the time of clinical detection of cancer after the exposure was affected by latency. The model predicted an increase in cancer risk in older adults caused by cell expansion and common background mutations. However, the risk in older adults was overestimated in the case of common ICC; this divergence could influence occupational ICC cases. Conclusions Three-stage ICC carcinogenesis has been proposed. The high mutation burden levels caused by occupational exposure led to an immediate incidence of cancer. After a long period of relatively low cancer risk, an increased risk in older adults was also predicted.

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Computational modeling of locoregional recurrence with spatial structure identifies tissue-specific carcinogenic profiles

Cited by 3 publications

References 71 publications

Exploring racial disparities in bladder urothelial cancer: insights into survival and genetic variations

Exploring racial disparities in bladder urothelial cancer: insights into survival and genetic variations

Patient-specific computational models predict prognosis in B cell lymphoma by quantifying pro-proliferative and anti-apoptotic signatures from genetic sequencing data

Multistage carcinogenesis in occupational cholangiocarcinoma: the impact of clonal expansion and risk estimation

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