Colorectal Adenoma Subtypes Exhibit Signature Molecular Profiles: Unique Insights into the Microenvironment of Advanced Precancerous Lesions for Early Detection Applications.
Simple Summary: Colorectal cancer originates from benign growths in the colon known as adenomas. Understanding how these adenomas become malignant is crucial to the early detection and prevention of colorectal cancer. This study examines DNA methylation and genetic differences among various types of...
| Publicado en: | Cancers Vol. 17; no. 4; pp. 654 - 673 |
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| Autores principales: | , , , , , , |
| Formato: | equations & formulas pictorial research tables/charts Journal Article |
| Publicado: |
MDPI
Feb2025
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=183336417&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 183336417 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 20726694 B74B jtl: Cancers issn: 20726694 maglogo: N pubinfo: dt: Feb2025 vid: 17 iid: 4 pid: 97109 pub: MDPI artinfo: ui: 183336417 183336417 183336417 10.3390/cancers17040654 183336417 ppf: 654 ppct: 19 formats: tig: atl: Colorectal Adenoma Subtypes Exhibit Signature Molecular Profiles: Unique Insights into the Microenvironment of Advanced Precancerous Lesions for Early Detection Applications. aug: au: Mancuso, Francesco Mattia Higareda-Almaraz, Juan Carlos Canal-Noguer, Pol Bertossi, Arianna Perera-Lluna, Alexandre Roehrl, Michael Herbert Alexander Kruusmaa, Kristi affil: Universal Diagnostics S.A., 41013 Seville, Spain sug: subj: Colorectal Neoplasms Physiopathology Adenoma Physiopathology Cell Physiology Precancerous Conditions Classification Early Detection of Cancer Colorectal Neoplasms Prevention and Control Neoplasm Staging Genomics Mutation Funding Source Human Methylation Evaluation Disease Progression Signal Transduction Stem Cells Physiology Wnt Proteins Physiology Chromosomes Adenoma Drug Therapy Colorectal Neoplasms Drug Therapy ab: Simple Summary: Colorectal cancer originates from benign growths in the colon known as adenomas. Understanding how these adenomas become malignant is crucial to the early detection and prevention of colorectal cancer. This study examines DNA methylation and genetic differences among various types of advanced adenomas to identify potential markers that indicate progression toward cancer. By analyzing DNA methylation patterns, gene copy-number changes, and mutations in these lesions, particular signals and pathways associated with each subtype were found. These discoveries can help refine screening methods to detect distinct adenomas lesions at an early stage. By providing new insights into the initial changes leading to colorectal cancer, these findings may significantly impact approaches to prevention and early intervention strategies. Background: Colorectal cancer (CRC) is characterized by the uncontrolled growth of malignant colonic or rectal crypt epithelium. About 85% of CRCs evolve through a stepwise progression from advanced precancerous adenoma lesions. A better understanding of the evolution from adenoma to carcinoma can provide a window of opportunity not only for early detection and therapeutic intervention but potentially also for cancer prevention strategies. Methods: This study investigates the heterogeneous methylation, copy-number alteration (CNA), and mutation signals of histological adenoma subtypes in the context of progression from normal colon to advanced precancerous lesions (APLs) and early-stage CRC. Results: Differential methylation analysis revealed 2321 significantly altered regions among APLs: 137 hypermethylated regions in serrated vs. tubular, 2093 in serrated vs. tubulovillous, and 91 in tubular vs. tubulovillous adenoma subtypes. The most differentiating pathways for serrated adenomas belonged to cAMP signaling and the regulation of pluripotency of stem cells, while regions separating tubular and tubulovillous subtypes were enriched for WNT signaling. CNA events were mostly present in tubular or tubulovillous adenomas, with the most frequent signals being seen in chromosomes 7, 12, 19, and 20. In contrast, early-stage CRC exhibited signals in chromosomes 7, 8, and 20, indicating different processes between APL and early-stage CRC. Mutations reinforce subtype-level differences, showing specific alterations in each subtype. Conclusions: These findings are especially important for developing early detection or cancer prevention tests trying to capture adenoma signatures. pubtype: Academic Journal doctype: equations & formulas pictorial research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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