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Updated: Jul 5, 2025
Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer
Published on: September 18, 2020
Genome-Wide Analysis of DNA Methylation in Pseudomyxoma Peritonei Originated from Appendiceal Neoplasms
Kiyoko Takane1, Tingwei Cai2, Rei Noguchi3
1Clinical Genome Research, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan, ktakane@g.ecc.u-tokyo.ac.jp.
Introduction:
Pseudomyxoma peritonei (PMP) is a disease characterized by progressive accumulation of intraperitoneal mucinous ascites produced by neoplasms in the abdominal cavity. Since the prognosis of patients with PMP remains unsatisfactory, the development of effective therapeutic drug(s) is a matter of pressing concern. Genetic analyses of PMP have clarified the frequent activation of GNAS and/or KRAS. However, the involvement of global epigenetic alterations in PMPs has not been reported.
Methods:
To clarify the genetic background of the 15 PMP tumors, we performed genetic analysis using AmpliSeq Cancer HotSpot Panel v2. We further investigated global DNA methylation in the 15 tumors and eight noncancerous colonic epithelial tissues using MethylationEPIC array BeadChip (Infinium 850k) containing a total of 865,918 probes.
Results:
This is the first report of comprehensive DNA methylation profiles of PMPs in the world. We clarified that the 15 PMPs could be classified into at least two epigenotypes, unique methylation epigenotype (UME) and normal-like methylation epigenotype (NLME), and that genes associated with neuronal development and synaptic signaling may be involved in the development of PMPs. In addition, we identified a set of hypermethylation marker genes such as HOXD1 and TSPYL5 in the 15 PMPs.
Conclusions:
These findings may help the understanding of the molecular mechanism(s) of PMP and contribute to the development of therapeutic strategies for this life-threatening disease.
Insights
This study reveals distinct DNA methylation patterns in pseudomyxoma peritonei (PMP), classifying tumors into unique and normal-like epigenotypes. These findings offer new insights into PMP development and potential therapeutic targets for this rare cancer.
Area of Science:
- Oncology
- Epigenetics
- Genomics
Background:
- Pseudomyxoma peritonei (PMP) is a rare abdominal cancer characterized by mucinous ascites.
- Current PMP prognoses are poor, necessitating novel therapeutic strategies.
- Previous research identified frequent GNAS and KRAS gene activation, but global epigenetic alterations remain unexplored.
Purpose of the Study:
- To comprehensively analyze DNA methylation profiles in PMP tumors.
- To identify novel epigenetic markers and understand the molecular basis of PMP.
Main Methods:
- Genetic analysis of 15 PMP tumors using AmpliSeq Cancer HotSpot Panel v2.
- Global DNA methylation profiling of 15 PMP tumors and 8 noncancerous tissues via MethylationEPIC array (Infinium 850k).
Main Results:
- This is the first global DNA methylation analysis of PMP.
- PMP tumors were classified into at least two epigenotypes: unique methylation epigenotype (UME) and normal-like methylation epigenotype (NLME).
- Genes involved in neuronal development and synaptic signaling may play a role in PMP pathogenesis. HOXD1 and TSPYL5 were identified as hypermethylated marker genes.
Conclusions:
- The identified epigenotypes and associated genes advance the understanding of PMP molecular mechanisms.
- These findings may facilitate the development of targeted therapies for PMP.
- This research provides a foundation for future epigenetic studies in PMP.
