Resolving genetic heterogeneity in cancer

Nature Reviews Genetics, Journal Year: 2019, Volume and Issue: 20(7), P. 404 - 416

Published: March 27, 2019

Language: Английский

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Colorectal Cancer: Genetic Abnormalities, Tumor Progression, Tumor Heterogeneity, Clonal Evolution and Tumor-Initiating Cells

Medical Sciences, Journal Year: 2018, Volume and Issue: 6(2), P. 31 - 31

Published: April 13, 2018

Colon cancer is the third most common worldwide. Most colorectal occurrences are sporadic, not related to genetic predisposition or family history; however, 20-30% of patients with have a history and 5% these tumors arise in setting Mendelian inheritance syndrome. In many patients, development preceded by benign neoplastic lesion: either an adenomatous polyp serrated polyp. Studies carried out last years characterized main molecular alterations occurring cancers, showing that tumor each patient displays from two eight driver mutations. The ensemble studies, including gene expression has led proposed classifications identification four/five non-overlapping groups. homeostasis rapidly renewing intestinal epithelium ensured few stem cells present at level base crypts. Various experimental evidence suggests cancers may derive malignant transformation acquire cell properties following transformation. seem be involved chemoresistance, radioresistance relapse.

Language: Английский

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Detecting repeated cancer evolution from multi-region tumor sequencing data

Nature Methods, Journal Year: 2018, Volume and Issue: 15(9), P. 707 - 714

Published: Aug. 21, 2018

Language: Английский

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Subclonal reconstruction of tumors by using machine learning and population genetics

Nature Genetics, Journal Year: 2020, Volume and Issue: 52(9), P. 898 - 907

Published: Sept. 1, 2020

Language: Английский

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A temporal shift of the evolutionary principle shaping intratumor heterogeneity in colorectal cancer

Nature Communications, Journal Year: 2018, Volume and Issue: 9(1)

Published: July 17, 2018

Advanced colorectal cancer harbors extensive intratumor heterogeneity shaped by neutral evolution; however, in precancerous lesions has been poorly studied. We perform multiregion whole-exome sequencing on ten early tumors, which contained adenoma and carcinoma situ. By comparing with data from advanced we show that the tumors accumulate a higher proportion of subclonal driver mutations than is highlighted KRAS APC. also demonstrate variant allele frequencies tend to be suggesting are subject selective sweep tumorigenesis while evolution dominant ones. This study establishes evolutionary principle underlying shifts Darwinian during tumor progression.

Language: Английский

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Deep Learning in Cancer Diagnosis and Prognosis Prediction: A Minireview on Challenges, Recent Trends, and Future Directions

Computational and Mathematical Methods in Medicine, Journal Year: 2021, Volume and Issue: 2021, P. 1 - 28

Published: Oct. 31, 2021

Deep learning (DL) is a branch of machine and artificial intelligence that has been applied to many areas in different domains such as health care drug design. Cancer prognosis estimates the ultimate fate cancer subject provides survival estimation subjects. An accurate timely diagnostic prognostic decision will greatly benefit DL emerged technology choice due availability high computational resources. The main components standard computer-aided design (CAD) system are preprocessing, feature recognition, extraction selection, categorization, performance assessment. Reduction costs associated with sequencing systems offers myriad opportunities for building precise models diagnosis prediction. In this survey, we provided summary current works where helped determine best prediction tasks. generic model requiring minimal data manipulations achieves better results while working enormous volumes data. Aims scrutinize influence using histopathology images, present state-of-the-art methods, give directions future researchers refine existing methods.

Language: Английский

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Histone Modifications and their Role in Epigenetics of Cancer

Current Medicinal Chemistry, Journal Year: 2021, Volume and Issue: 29(14), P. 2399 - 2411

Published: Nov. 9, 2021

Epigenetic regulations play a crucial role in the expression of various genes that are important normal cell function. Any alteration these epigenetic mechanisms can lead to modification histone and DNA, resulting silencing or enhanced some causing diseases. Acetylation, methylation, ribosylation, phosphorylation proteins modifies its interaction with consequently changing ratio heterochromatin euchromatin. Terminal lysine residues serve as potential targets such modifications. The current review focuses on modifications, their contributing factors; modifications metabolism leads cancer, methylation cancer affects DNA repair mechanisms.

Language: Английский

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Neuroblastoma arises in early fetal development and its evolutionary duration predicts outcome

Nature Genetics, Journal Year: 2023, Volume and Issue: 55(4), P. 619 - 630

Published: March 27, 2023

Abstract Neuroblastoma, the most frequent solid tumor in infants, shows very diverse outcomes from spontaneous regression to fatal disease. When these different tumors originate and how they evolve are not known. Here we quantify somatic evolution of neuroblastoma by deep whole-genome sequencing, molecular clock analysis population-genetic modeling a comprehensive cohort covering all subtypes. We find that across entire clinical spectrum begin develop via aberrant mitoses as early first trimester pregnancy. Neuroblastomas with favorable prognosis expand clonally after short evolution, whereas aggressive neuroblastomas show prolonged during which acquire telomere maintenance mechanisms. The initial aneuploidization events condition subsequent exhibiting genomic instability. discovery ( n = 100), validate an independent 86), duration is accurate predictor outcome. Thus, insight into may prospectively guide treatment decisions.

Language: Английский

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Lipid metabolism and its implications in tumor cell plasticity and drug resistance: what we learned thus far?

Cancer and Metastasis Reviews, Journal Year: 2024, Volume and Issue: 43(1), P. 293 - 319

Published: March 1, 2024

Metabolic reprogramming, a hallmark of cancer, allows cancer cells to adapt their specific energy needs. The Warburg effect benefits in both hypoxic and normoxic conditions is well-studied reprogramming metabolism cancer. Interestingly, the alteration other metabolic pathways, especially lipid has also grabbed attention scientists worldwide. Lipids, primarily consisting fatty acids, phospholipids cholesterol, play essential roles as structural component cell membrane, signalling molecule reserves. This involves aberrations uptake, synthesis breakdown lipids, thereby contributing survival, proliferation, invasion, migration metastasis cells. development resistance existing treatment modalities poses major challenge field therapy. Also, plasticity tumor was reported be factor for resistance. A number studies implicated that dysregulated contributes associated drug Therefore, it important understand intricate In this review, we mainly focused on implication disturbed events inducing plasticity-mediated addition, discussed concept peroxidation its crucial role phenotypic switching ferroptosis Elucidating relationship between metabolism, emergence will open new opportunities develop innovative strategies combinatorial approaches

Language: Английский

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Natural bioactive compounds targeting DNA methyltransferase enzymes in cancer: Mechanisms insights and efficiencies

Chemico-Biological Interactions, Journal Year: 2024, Volume and Issue: 392, P. 110907 - 110907

Published: Feb. 21, 2024

The regulation of gene expression is fundamental to health and life essentially carried out at the promoter region DNA each gene. Depending on molecular context, this may be accessible or non-accessible (possibility integration RNA polymerase not region). Among enzymes that control process, methyltransferase (DNMTs), are responsible for demethylation CpG islands, particularly regions, regulate transcription. aberrant activity these enzymes, i.e. their abnormal activity, can result in repression overactivation expression. Consequently, generate cellular dysregulation leading instability tumor development. Several reports highlighted involvement DNMTs human cancers. inhibition activation a promising therapeutic approach many In present work, we provide comprehensive critical summary natural bioactive molecules as primary inhibitors active compounds hold potential developed anti-cancer epidrugs targeting DNMTs.

Language: Английский

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