Discovering the Mutational Profile of Early Colorectal Lesions: A Translational Impact

Alquati, Chiara; Prossomariti, Anna; Piazzi, Giulia; Buttitta, Francesco; Bazzoli, Franco; Laghi, Luigi; Ricciardiello, Luigi

doi:10.3390/cancers13092081

Cited by 4 publications

(1 citation statement)

References 82 publications

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“…Sequencing of 128 TSAs showed 97% harboured mutations in MAPK pathway genes (predominantly BRAF V600E or KRAS ) and 84% had mutations in WNT pathway genes [ 35 ]. Among WNT pathway genes, R-Spondin ( RSPO ) gene fusions and overexpression is frequently observed [ 36 ].…”

Section: Gene Mutations In Colorectal Polypsmentioning

confidence: 99%

Genomic, Microbial and Immunological Microenvironment of Colorectal Polyps

Tse

Welham

Engel

et al. 2021

Cancers

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Colorectal cancer (CRC) develops from pre-cancerous cellular lesions in the gut epithelium, known as polyps. Polyps themselves arise through the accumulation of mutations that disrupt the function of key tumour suppressor genes, activate proto-oncogenes and allow proliferation in an environment where immune control has been compromised. Consequently, colonoscopic surveillance and polypectomy are central pillars of cancer control strategies. Recent advances in genomic sequencing technologies have enhanced our knowledge of key driver mutations in polyp lesions that likely contribute to CRC. In accordance with the prognostic significance of Immunoscores for CRC survival, there is also a likely role for early immunological changes in polyps, including an increase in regulatory T cells and a decrease in mature dendritic cell numbers. Gut microbiotas are under increasing research interest for their potential contribution to CRC evolution, and changes in the gut microbiome have been reported from analyses of adenomas. Given that early changes to molecular components of bowel polyps may have a direct impact on cancer development and/or act as indicators of early disease, we review the molecular landscape of colorectal polyps, with an emphasis on immunological and microbial alterations occurring in the gut and propose the potential clinical utility of these data.

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Section: Gene Mutations In Colorectal Polypsmentioning

confidence: 99%

Genomic, Microbial and Immunological Microenvironment of Colorectal Polyps

Tse

Welham

Engel

et al. 2021

Cancers

View full text Add to dashboard Cite

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Immune profiling of premalignant lesions in patients with Peutz‐Jeghers syndrome

Liu,

Wu,

Shi

et al. 2024

UEG Journal

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BackgroundPeutz‐Jeghers syndrome (PJS), is a rare autosomal dominant hereditary disease characterized by an elevated risk of various cancers. Serine/Threonine Kinase 11 (STK11) gene is a major tumor suppressor crucial for immune evasion with and beyond tumorigenic cells. It has garnered increasing attention in the realm of oncology treatment, particularly in the context of immunotherapy development.ObjectiveThis study aimed to assess the suitability of polyps obtained from individuals with PJS, resulting from germline STK11 deficiency, for immunotherapy. Additionally, we seek to identify potential shared mechanisms related to immune evasion between PJS polyps and cancers. To achieve this, we examined PJS polyps alongside familial adenomatous polyposis (FAP) and sporadic polyps.MethodsPolyps were compared among themselves and with either the paracancerous tissues or colon cancers. Pathological and gene expression profiling approaches were employed to characterize infiltrating immune cells and assess the expression of immune checkpoint genes.ResultsOur findings revealed that PJS polyps exhibited a closer resemblance to cancer tissues than other polyps in terms of their immune microenvironment. Notably, PJS polyps displayed heightened expression of the immune checkpoint gene CD80 and an accumulation of myeloid cells, particularly myeloid‐derived suppressor cells (MDSCs).ConclusionThe findings suggest an immunobiological foundation for the increased cancer susceptibility in PJS patients, paving the way for potential immune therapy applications in this population. Furthermore, utilizing PJS as a model may facilitate the exploration of immune evasion mechanisms, benefiting both PJS and cancer patients.

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