Small Bowel Epithelial Precursor Lesions: A Focus on Molecular Alterations
Abstract
:1. Introduction
2. Sporadic Small Bowel Dysplastic Glandular Lesions
2.1. Non-Ampullary Duodenal Adenomas
2.1.1. Intestinal-Type Adenomas
2.1.2. Gastric-Type Adenomas
2.2. Ampullary Preinvasive Neoplasms
2.2.1. Ampullary Duodenal Adenomas
2.2.2. Intra-Ampullary Papillary-Tubular Neoplasms
3. Small Bowel Adenomas in Hereditary Syndromes
4. Premalignant Epithelial Lesions in Celiac Disease and Crohn’s Disease
4.1. Celiac Disease
4.2. Crohn’s Disease
5. Serrated Lesions
6. Hamartomatous Lesions
7. Duodenal Neuroendocrine Lesions in Multiple Endocrine Neoplasia Type 1 (MEN1)
8. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Subtype | Gene (Encoded Protein) | Prevalence of Mutations | Functional Effect | |
---|---|---|---|---|
Sporadic, non-ampullary, intestinal-type adenomas | APC (Adenomatous polyposis coli protein) | 50–55% [15,16] | Regulation of Wnt signaling pathway, cell migration and adhesion, apoptosis | |
KRAS (KRas) | 5–18% [15,16] | GTPase intracellular signal transducer, regulating proliferation and differentiation | ||
BRAF (BRaf) | 0–4% [16] | Activation of the MAP kinase transduction pathway | ||
ERBB2/HER2 (erbB2) | <5% [16] | Protein tyrosine kinase involved in stabilization of peripheral microtubules and transcriptional regulation | ||
TP53 (p53) | <5% [15,16] | Regulation of cell cycle arrest, apoptosis, senescence and DNA repair | ||
Pyloric gland adenomas | GNAS (G-alpha subunits of G proteins) | 40% [27] | GPCR-mediated signaling constitutively active; PKA activation | |
Foveolar adenomas | GNAS (G-alpha subunits of G proteins) | 100% [27] | GPCR-mediated signaling constitutively active; PKA activation | |
Sporadic, ampullary, intestinal-type adenomas | APC (Adenomatous polyposis coli protein) | 17–44% [15,52] | Regulation of Wnt signaling pathway, cell migration and adhesion, apoptosis | |
KRAS (KRas) | 30–44% [15,55,56] | GTPase, intracellular signal transducer, regulating proliferation and differentiation | ||
Syndromic intestinal-type adenomas | FAP | APC (Adenomatous polyposis coli protein) | 17–66% [15,52,96] | Regulation of Wnt signaling pathway, cell migration and adhesion, apoptosis |
KRAS (KRas) | 10% [96] | GTPase, intracellular signal transducer, regulating proliferation and differentiation | ||
MAP | MUTYH (Adenine DNA glycosilase) | 100% | Oxidative DNA damage repair (base excision repair) | |
APC (Adenomatous polyposis coli protein) | 77% [96] | Regulation of Wnt signaling pathway, cell migration and adhesion, apoptosis | ||
KRAS (KRas) | 33% [96] | GTPase, intracellular signal transducer, regulating proliferation and differentiation | ||
Crohn’s disease-associated dysplasia | KRAS (KRas) | 15–40% [113,115] | GTPase, intracellular signal transducer, regulating proliferation and differentiation | |
PIK3CA (Phosphatidylinositol 4,5-biphosphate 3-kinase catalytic subunit alpha isoform) | 0–60% [113,115] | Activation of cell signaling regulating cellular growth, proliferation and morphology | ||
Peutz-Jeghers polyps | STK11 (STK11) | >90% [143] | Tumor suppressor serine/threonine-protein kinase, controlling AMPK family members | |
Juvenile polyps | SMAD4 (Smad4/Dpc4) | 20% [151] | Tumor suppressor, mediator of signal transduction by TGF β | |
BMPR1A (Bone morphogenetic protein receptor type-1A) | 30% [151] | Transmembrane serine/threonine kinases, activation of SMAD transcriptional regulators | ||
Cowden syndrome polyps | PTEN (Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase) | 80% [154] | Tumor suppressor related to the mTOR pathway through downregulation of the PI3K signaling pathway |
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Vanoli, A.; Grillo, F.; Furlan, D.; Arpa, G.; Grami, O.; Guerini, C.; Riboni, R.; Mastracci, L.; Di Sabatino, A. Small Bowel Epithelial Precursor Lesions: A Focus on Molecular Alterations. Int. J. Mol. Sci. 2021, 22, 4388. https://doi.org/10.3390/ijms22094388
Vanoli A, Grillo F, Furlan D, Arpa G, Grami O, Guerini C, Riboni R, Mastracci L, Di Sabatino A. Small Bowel Epithelial Precursor Lesions: A Focus on Molecular Alterations. International Journal of Molecular Sciences. 2021; 22(9):4388. https://doi.org/10.3390/ijms22094388
Chicago/Turabian StyleVanoli, Alessandro, Federica Grillo, Daniela Furlan, Giovanni Arpa, Oneda Grami, Camilla Guerini, Roberta Riboni, Luca Mastracci, and Antonio Di Sabatino. 2021. "Small Bowel Epithelial Precursor Lesions: A Focus on Molecular Alterations" International Journal of Molecular Sciences 22, no. 9: 4388. https://doi.org/10.3390/ijms22094388