Molecular Profiling of Low‐Grade Appendiceal Mucinous Neoplasms (LAMN) DOI Creative Commons
Julia Doll, Katja Maurus,

Franziska Köhler

et al.

Genes Chromosomes and Cancer, Journal Year: 2024, Volume and Issue: 63(10)

Published: Oct. 1, 2024

ABSTRACT Low‐grade appendiceal mucinous neoplasia (LAMN) represents a relatively rare tumor of the appendix typically diagnosed incidentally through appendectomy for acute appendicitis. In cases where perforation occurs, content may disseminate into abdominal cavity, leading to development pseudomyxoma peritonei (PMP). The primary objective this study was elucidate molecular characteristics associated with various stages LAMN and PMP. DNA extracted from LAMN, PMPs, recurrent adenocarcinomas originating LAMN. subsequent analysis involved examination mutational hotspot regions within 50 cancer‐related genes, covering over 2800 COSMIC mutations, utilizing amplicon‐based next‐generation sequencing (NGS). Our findings revealed activating somatic mutations MAPK‐signaling pathway across all tumors examined. Specifically, 98.1% showed in KRAS , while one harbored BRAF mutation. Additionally, GNAS were identified 55.8% tumors, no significant difference observed between While rarely displayed additional 42% PMPs 60% mutations. Notably, both TP53 . Furthermore, 7.7% (4/52) exhibited potentially targetable G12C four patients, NGS performed on PMP PMP/adenocarcinoma samples. detected almost samples, 50% an SMAD4 mutation, suggesting notable alteration during disease progression. indicate two key points: First, MAPK pathway, particularly are evident along high frequency Second, progression toward or adenocarcinoma is accumulation common oncogenic pathways.

Language: Английский

Gene expression profiling to uncover prognostic and therapeutic targets in colon cancer, combined with docking and dynamics studies to discover potent anticancer inhibitor DOI

Mohammad Kashif

Computational Biology and Chemistry, Journal Year: 2025, Volume and Issue: 115, P. 108349 - 108349

Published: Jan. 9, 2025

Language: Английский

Citations

0
Contract to kill: GNAS mutation DOI Creative Commons

Pratima Raut,

Poompozhil Mathivanan,

Surinder K. Batra

et al.

Molecular Cancer, Journal Year: 2025, Volume and Issue: 24(1)

Published: March 7, 2025

The mutation in Gsα-coding GNAS exons, popular as gsp oncogene, is the most frequent across all heterotrimeric G proteins involved oncogenesis. R201, frequently mutated, followed by Q227, are found predominantly various neoplasms and cancers such IPMN, pituitary, thyroid, appendiceal, colorectal, etc. This review emphasizes pivotal significance of oncogene its ramifications underpinning sustained addiction to mutation. Recent studies delineating mechanistic intricacies that provide solid evidence profound impact oncogenic on tumor formation, progression, maintenance highlighted. We have leveraged discoveries Gsα an ideal neoantigen candidate for vaccine therapy, allele-specific inhibitors, cyclic peptide-based small molecular inhibitors explored therapeutic potential target directly. Alternative modalities patient-centric mitigate mutations also discussed. exposition novel strategies designed address challenges inherent these approaches targeting activating GNAS, along with probable avenues further investigation, aims reverberate current understanding genomic biological landscape GNAS-driven cancers, against them.

Language: Английский

Citations

0
The multifaceted role of phosphodiesterase 4 in tumor: from tumorigenesis to immunotherapy DOI Creative Commons

Huimin Ren,

Shaohui Zhang, Peiyuan Li

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: March 10, 2025

Phosphodiesterase 4 (PDE4) is an enzyme that specifically hydrolyzes the second messenger cAMP and has a critical role in regulation of variety cellular functions. In recent years, PDE4 attracted great interest cancer research, its tumorigenesis development been gradually elucidated. Research indicates abnormal expression or heightened activity associated with initiation progression multiple cancers, including lung, colorectal, hematological by facilitating cell proliferation, migration, invasion, anti-apoptosis. Moreover, also influences tumor immune microenvironment, significantly evasion suppressing anti-tumor responses, reducing T-cell activation, promoting polarization tumor-associated macrophages toward pro-tumorigenic phenotype. However, family may have both oncogenic tumor-suppressive effects, which could depend on specific type grade tumor. inhibitors garnered substantial as potential anti-cancer therapeutics, directly inhibiting growth restoring surveillance capabilities to enhance clearance cells. Several are currently under investigation aim exploring their therapy, particularly combination strategies checkpoint inhibitors, improve therapeutic efficacy mitigate side effects conventional chemotherapy. This review provides overview tumorigenesis, drug resistance, immunotherapy, actions intending guide exploration new target therapy.

Language: Английский

Citations

0
Proteome-wide assessment of differential missense variant clustering in neurodevelopmental disorders and cancer DOI Creative Commons

Jeffrey K. Ng,

Yilin Chen,

Titilope M. Akinwe

et al.

Cell Genomics, Journal Year: 2025, Volume and Issue: unknown, P. 100807 - 100807

Published: March 1, 2025

Language: Английский

Citations

0
Expression Pattern of PDE4B, PDE4D, and SFRP5 Markers in Colorectal Cancer DOI Creative Commons
Mateo Bevanda, Nela Kelam,

Anita Racetin

et al.

Medicina, Journal Year: 2024, Volume and Issue: 60(8), P. 1202 - 1202

Published: July 25, 2024

Background and Objectives: Colorectal cancer (CRC) is the most frequently diagnosed malignant disease of gastrointestinal system, new diagnostic prognostic markers are needed to elucidate complete tumor profile. Materials Methods: We used CRC tissues (Dukes’ A-D) adjacent noncancerous 43 patients. Immunohistochemistry was examine expression phosphodiesterase 4B (PDE4B), 4D (PDE4D), secreted frizzled related protein 5 (SFRP5) markers. also analyzed levels PDE4B, PDE4D, SFRP5 in compared control using RNA-sequencing data from UCSC Xena browser. Results: In stages, distribution PDE4B-positive cells varied, with differing percentages between epithelium lamina propria. Statistically significant differences were found number epithelial healthy controls all as well different stages. Similarly, observed propria stage Dukes’ C exhibited a significantly higher B. Significant noted PDE4D-positive stages A, B, D, D. A had more SFRP5-positive While PDE4D varied across remained consistently strong both propria, mainly The reveal these genes patients controls, notable implications for patient prognosis. Namely, our results demonstrate that under-expressed tissues. Kaplan–Meier survival analysis log-rank (Mantel–Cox) test revealed distinct where lower longer overall survival. align immunohistochemical might suggest potential tumor-suppressive role CRC. Conclusions: Considering gene expression, aligned tissue comparison tissue, poorer rate case its we can hypothesize promising biomarker out proteins. These findings alterations during progression, CRC, understanding molecular mechanisms involved development progression.

Language: Английский

Citations

2
Going Rogue: Mechanisms, Regulation, and Roles of Mutationally Activated Gαin Human Cancer DOI

Morgan Dwyer,

Jenna Aumiller, Philip Wedegaertner

et al.

Molecular Pharmacology, Journal Year: 2024, Volume and Issue: 106(5), P. 198 - 215

Published: Aug. 26, 2024

G protein-coupled receptors (GPCRs) couple to heterotrimeric proteins, comprised of

Language: Английский

Citations

2
Molecular Profiling of Low‐Grade Appendiceal Mucinous Neoplasms (LAMN) DOI Creative Commons
Julia Doll, Katja Maurus,

Franziska Köhler

et al.

Genes Chromosomes and Cancer, Journal Year: 2024, Volume and Issue: 63(10)

Published: Oct. 1, 2024

ABSTRACT Low‐grade appendiceal mucinous neoplasia (LAMN) represents a relatively rare tumor of the appendix typically diagnosed incidentally through appendectomy for acute appendicitis. In cases where perforation occurs, content may disseminate into abdominal cavity, leading to development pseudomyxoma peritonei (PMP). The primary objective this study was elucidate molecular characteristics associated with various stages LAMN and PMP. DNA extracted from LAMN, PMPs, recurrent adenocarcinomas originating LAMN. subsequent analysis involved examination mutational hotspot regions within 50 cancer‐related genes, covering over 2800 COSMIC mutations, utilizing amplicon‐based next‐generation sequencing (NGS). Our findings revealed activating somatic mutations MAPK‐signaling pathway across all tumors examined. Specifically, 98.1% showed in KRAS , while one harbored BRAF mutation. Additionally, GNAS were identified 55.8% tumors, no significant difference observed between While rarely displayed additional 42% PMPs 60% mutations. Notably, both TP53 . Furthermore, 7.7% (4/52) exhibited potentially targetable G12C four patients, NGS performed on PMP PMP/adenocarcinoma samples. detected almost samples, 50% an SMAD4 mutation, suggesting notable alteration during disease progression. indicate two key points: First, MAPK pathway, particularly are evident along high frequency Second, progression toward or adenocarcinoma is accumulation common oncogenic pathways.

Language: Английский

Citations

2