Familial Adenomatous Polyposis or APC-Associated Polyposis

Nielsen, Maartje; Aretz, Stephan

doi:10.1007/978-3-319-74259-5_7

Cited by 8 publications

(3 citation statements)

References 69 publications

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“…In addition to Lynch syndrome colorectal carcinogenesis, we modify the ansatz to model the sporadic counterpart of Lynch syndrome, often called Lynch-like cancers [ 6 ], as well as the classical adenoma-carcinoma sequence first described by Vogelstein and Kinzler [ 7 ] for microsatellite-stable (MSS) CRCs. Further, we apply the model to another hereditary CRC syndrome, familial adenomatous polyposis (FAP) [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Mathematical modeling of multiple pathways in colorectal carcinogenesis using dynamical systems with Kronecker structure

et al. 2021

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Like many other types of cancer, colorectal cancer (CRC) develops through multiple pathways of carcinogenesis. This is also true for colorectal carcinogenesis in Lynch syndrome (LS), the most common inherited CRC syndrome. However, a comprehensive understanding of the distribution of these pathways of carcinogenesis, which allows for tailored clinical treatment and even prevention, is still lacking. We suggest a linear dynamical system modeling the evolution of different pathways of colorectal carcinogenesis based on the involved driver mutations. The model consists of different components accounting for independent and dependent mutational processes. We define the driver gene mutation graphs and combine them using the Cartesian graph product. This leads to matrix components built by the Kronecker sum and product of the adjacency matrices of the gene mutation graphs enabling a thorough mathematical analysis and medical interpretation. Using the Kronecker structure, we developed a mathematical model which we applied exemplarily to the three pathways of colorectal carcinogenesis in LS. Beside a pathogenic germline variant in one of the DNA mismatch repair (MMR) genes, driver mutations in APC, CTNNB1, KRAS and TP53 are considered. We exemplarily incorporate mutational dependencies, such as increased point mutation rates after MMR deficiency, and based on recent experimental data, biallelic somatic CTNNB1 mutations as common drivers of LS-associated CRCs. With the model and parameter choice, we obtained simulation results that are in concordance with clinical observations. These include the evolution of MMR-deficient crypts as early precursors in LS carcinogenesis and the influence of variants in MMR genes thereon. The proportions of MMR-deficient and MMR-proficient APC-inactivated crypts as first measure for the distribution among the pathways in LS-associated colorectal carcinogenesis are compatible with clinical observations. The approach provides a modular framework for modeling multiple pathways of carcinogenesis yielding promising results in concordance with clinical observations in LS CRCs.

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Section: Introductionmentioning

confidence: 99%

Mathematical modeling of multiple pathways in colorectal carcinogenesis using dynamical systems with Kronecker structure

et al. 2021

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“…In addition to the Lynch syndrome case, we modify the ansatz to model the sporadic counterpart of Lynch syndrome, often called Lynch-like cancers [Car14], as well as the classical adenoma-carcinoma sequence first described by Vogelstein and Kinzler [VK93] for microsatellite-stable (MSS) colorectal cancers. Further, we apply the model to another hereditary colorectal cancer syndrome, familial adenomatous polyposis (FAP) [NA18].…”

Section: Introductionmentioning

confidence: 99%

Mathematical Modeling of Multiple Pathways in Colorectal Carcinogenesis using Dynamical Systems with Kronecker Structure

Haupt

Zeilmann

Ahadova³

et al. 2020

Preprint

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Like many other tumors, colorectal cancers develop through multiple pathways containing different driver mutations. This is also true for colorectal carcinogenesis in Lynch syndrome, the most common inherited colorectal cancer syndrome. However, a comprehensive understanding of Lynch syndrome tumor evolution which allows for tailored clinical treatment and even prevention is still lacking. We suggest a linear autonomous dynamical system modeling the evolution of the different pathways. Starting with the gene mutation graphs of the driver genes, we formulate three key assumptions about how these different mutations might be combined. This approach leads to a dynamical system that is built by the Kronecker sum of the adjacency matrices of the gene mutation graphs. This Kronecker structure makes the dynamical system amenable to a thorough mathematical analysis and medical interpretation, even if the number of incorporated genes or possible mutation states is increased. For the case that some of the mathematical key assumptions are not satisfied, we explain possible extensions to our model. Additionally, improved bio-medical measurements or novel medical insights can be integrated into the model in a straightforward manner, as all parameters in the model have a biological interpretation. Modifications of the model are able to account for other forms of colorectal carcinogenesis, such as Lynch-like and familial adenomatous polyposis cases.

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“…Other syndromes that are strongly associated with colon cancer is Gardner syndrome. And familial adenomatous polyposis (FAP) [30], people with these syndromes develop colon cancer in 1% of the total cases [31].…”

Section: Genetics Causesmentioning

confidence: 99%

Lipoxygenase and Colon Cancer

Al-Adlee¹

2023

Current Topics in Colorectal Surgery

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Colon cancer is an abnormal growth of cells that occurs in the large intestine. Sometimes growth remains restricted for a relatively long time before it becomes a malignant tumor and then spreads through the intestinal wall to the lymph nodes and other parts of the body. The study aims to estimate the effectiveness and partial purification of lipoxygenase (LOX) enzyme and measure gamma-glutamyle transferase (GGT) activity in serum patients of colon cancer in Baghdad. The study included (80) case male patients with colon cancer with (50) samples of apparently healthy males (control) as comparison group. The result displayed a noteworthy increase in lipoxygenase effectiveness (805.0±517.23 IU/L) in serum of patients with colon cancer (T3 stage) compared with control (114.6±49.77 IU/L). The enzyme was purified by the precipitation of the serum protein using (40% (NH4)2SO4) then removing the remaining salts by dialysis. The column of gel (sephadex G.100) was used to separate the enzyme from another protein, in this step a single peak was obtained. The effective part of lipoxygenase at yield (71.42%) and folds (11.033). The ion exchange chromatography (DEAE–CeA50) was used to isolate LOX isoenzyme, two bands (LOX1 and LOX2) were acquired with different degree of purity (16.372) and (12.16) folds respectively. The result displayed a noteworthy increase in the (GGT) activity in patients (58.69±16.94IU/L) (probability P≤ 0.000) compared with control (12.79±5.68 IU/L). The increase in activity of LOX can be used as a tumor marker to detect the colon cancer disease.

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Familial Adenomatous Polyposis or APC-Associated Polyposis

Cited by 8 publications

References 69 publications

Mathematical modeling of multiple pathways in colorectal carcinogenesis using dynamical systems with Kronecker structure

Mathematical modeling of multiple pathways in colorectal carcinogenesis using dynamical systems with Kronecker structure

Mathematical Modeling of Multiple Pathways in Colorectal Carcinogenesis using Dynamical Systems with Kronecker Structure

Lipoxygenase and Colon Cancer

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