IBD-Associated Dysplastic Lesions Show More Chromosomal Instability Than Sporadic Adenomas

Wanders, Linda K; Cordes, Martijn; Voorham, Quirinus J.M.; Sie, Daoud; Vries, Sara D de; D’Haens, Geert; Boer, Nanne K. H. de; Ylstra, Bauke; Grieken, Nicole C.T. van; Meijer, Gerrit A.; Dekker, Evelien; Carvalho, Beatriz

doi:10.1093/ibd/izz171

Cited by 32 publications

(27 citation statements)

References 38 publications

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“…Developing therapeutic strategies that simultaneously target trunk and branch alterations is a relatively simple concept; however, CIN adds an additional layer of complexity that impacts the ability to accurately identify the exploitable genetic alterations. It is generally accepted that CIN is an early etiological event in the development of numerous cancer types, as it is detected in dysplastic/precancerous lesions [108,[152][153][154] and can induce cellular transformation [9,50]. Thus, CIN genes, or those genes whose aberrant expression induces CIN, are frequently viewed as trunk alterations [51,94].…”

Section: The Impact Of Cin On Therapeutic Targetingmentioning

confidence: 99%

Chromosome Instability; Implications in Cancer Development, Progression, and Clinical Outcomes

Vishwakarma

McManus

2020

Cancers

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Chromosome instability (CIN) refers to an ongoing rate of chromosomal changes and is a driver of genetic, cell-to-cell heterogeneity. It is an aberrant phenotype that is intimately associated with cancer development and progression. The presence, extent, and level of CIN has tremendous implications for the clinical management and outcomes of those living with cancer. Despite its relevance in cancer, there is still extensive misuse of the term CIN, and this has adversely impacted our ability to identify and characterize the molecular determinants of CIN. Though several decades of genetic research have provided insight into CIN, the molecular determinants remain largely unknown, which severely limits its clinical potential. In this review, we provide a definition of CIN, describe the two main types, and discuss how it differs from aneuploidy. We subsequently detail its impact on cancer development and progression, and describe how it influences metastatic potential with reference to cancer prognosis and outcomes. Finally, we end with a discussion of how CIN induces genetic heterogeneity to influence the use and efficacy of several precision medicine strategies, including patient and risk stratification, as well as its impact on the acquisition of drug resistance and disease recurrence.

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Section: The Impact Of Cin On Therapeutic Targetingmentioning

confidence: 99%

Chromosome Instability; Implications in Cancer Development, Progression, and Clinical Outcomes

Vishwakarma

McManus

2020

Cancers

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“…These patients were more likely to present with metastatic disease (29% compared to 9% with localised disease) [16]. This is especially significant as IBD-associated dysplastic lesions have been shown to be more genomically unstable, perhaps reflecting a faster progression towards cancer and greater metastatic potential [16,20].…”

Section: Risk Factorsmentioning

confidence: 99%

Sporadic colorectal cancer in adolescents and young adults: a scoping review of a growing healthcare concern

Christodoulides

Lami

Malietzis

et al. 2020

Int J Colorectal Dis

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Purpose Sporadic colorectal cancer (CRC) amongst adolescents and young adults (AYA) is increasing in incidence. The reasons for this trend are not well understood. Current guidelines do not specifically address this patient cohort. A scoping review was performed to summarise the range of available evidence and identify key areas that need to be addressed in current guidelines. Methods A systematic literature search was conducted adhering to the PRISMA statement. All potentially eligible studies were screened, and data extraction was performed by two reviewers independently. The studies were then divided into 5 broad subgroups: (1) risk factors, (2) screening, (3) clinicopathological and molecular features, (4) presentation and (5) management. Descriptive statistics were used for data analysis. Results A total of 17 studies were included from 2010 to 2019. Overall, young adults with CRC tend to present with non-specific symptoms. The majority of these patients have a delayed diagnosis and more advanced disease at presentation, with a rise in prevalence of distal colon and rectal cancers. AYAs tend to have poorly differentiated tumours and are managed more aggressively. Overall 5-year survival varies between studies. Conclusion This is, to our knowledge, the first scoping review presenting the range of available evidence on CRC in AYAs. Although the rise in incidence is recognised by specialist bodies, recommendations are limited by the sparsity of available data. We seek to highlight the need for further research, define the role of earlier screening and raise awareness to promote thorough assessment of young patients.

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“…IBD is a group of chronic, non‐specific and diffuse inflammatory diseases that occur in the gastrointestinal tract 1 . IBD is manifested by recurrent attack, poor drug efficacy, high risk of developing related complications and high disability rate 2 .…”

Section: Introductionmentioning

confidence: 99%

“…IBD is a group of chronic, non-specific and diffuse inflammatory diseases that occur in the gastrointestinal tract. 1 IBD is manifested by recurrent attack, poor drug efficacy, high risk of developing related complications and high disability rate. 2 The conventional treatments for IBD include glucocorticoid, salicylazosulfapyridine/5aminosalicylic acid and biological agents, which, however, have limited effectiveness because of low specificity, high prevalence of drug resistance and poor long-term efficacy.…”

Section: Introductionmentioning

confidence: 99%

Role of sphingosine‐1‐phosphate receptors in vascular injury of inflammatory bowel disease

Wang

Chen

Xiang

et al. 2021

J Cellular Molecular Medi

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Sphingosine‐1‐phosphate receptors (S1PRs) have an impact on the intestinal inflammation of inflammatory bowel disease (IBD) by regulating lymphocyte migration and differentiation. S1PR modulators as an emerging therapeutic approach are being investigated for the treatment of IBD. However, the role of S1PRs in intestinal vessels has not drawn much attention. Intestinal vascular damage is one of the major pathophysiological features of IBD, characterized by increased vascular density and impaired barrier function. S1PRs have pleiotropic effects on vascular endothelial cells, including proliferation, migration, angiogenesis and barrier homeostasis. Mounting evidence shows that S1PRs are abnormally expressed on intestinal vascular endothelial cells in IBD. Unexpectedly, S1PR modulators may damage intestinal vasculature, for example increase intestinal bleeding; therefore, S1PRs are thought to be involved in the regulation of intestinal vascular function in IBD. However, little is understood about how S1PRs regulate intestinal vascular function and participate in the initiation and progression of IBD. In this review, we summarize the pathogenic role of S1PRs in and the underlying mechanisms behind the intestinal vascular injury in IBD in order for improving IBD practice including S1PR‐targeted therapies.

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IBD-Associated Dysplastic Lesions Show More Chromosomal Instability Than Sporadic Adenomas

Cited by 32 publications

References 38 publications

Chromosome Instability; Implications in Cancer Development, Progression, and Clinical Outcomes

Chromosome Instability; Implications in Cancer Development, Progression, and Clinical Outcomes

Sporadic colorectal cancer in adolescents and young adults: a scoping review of a growing healthcare concern

Role of sphingosine‐1‐phosphate receptors in vascular injury of inflammatory bowel disease

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