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Peer-reviewedCC BY 4.0International Journal of Molecular Sciences

Beyond Mesothelioma: From Diagnostic Biomarker to Therapeutic Opportunity—The Emerging Role of MTAP in Cancer

  • Anna Diluvio1
  • Stefano Lucà1
  • Lucia Iavarone1
  • Valeria Masola1
  • Alfonso Fiorelli2
  • Floriana Morgillo3
  • Giuseppe D’Abbronzo1
  • Renato Franco1
  1. 1Pathology Unit, Department of Mental Health and Physic and Preventive Medicine University of Campania “L. Vanvitelli”, 80138 Naples, Italy
  2. 2Thoracic Surgery Unit, Department of Cardio-Thoracic and Respiratory Sciences, Università degli Studi Della Campania “Luigi Vanvitelli”, 80138 Naples, Italy
  3. 3Medical Oncology, Department of Precision Medicine, University of Campania “L. Vanvitelli”, 80138 Naples, Italy
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Abstract

Methylthioadenosine phosphorylase (MTAP) loss is an emerging biomarker in several human malignancies, mainly due to its frequent co-deletion with CDKN2A on chromosome 9p21. Beyond its diagnostic value, MTAP deficiency has important biological consequences, including metabolic reprogramming, immune microenvironment modulation, and increased dependency on PRMT5-related pathways. This review summarizes the current evidence on MTAP alterations across different tumor types. The role of MTAP immunohistochemistry as a practical surrogate for CDKN2A homozygous deletion is discussed, together with its advantages and interpretative limitations. In addition, the potential predictive relevance of MTAP loss for immunotherapy, antifolate-based treatments, and novel PRMT5-targeted strategies is explored. Overall, MTAP assessment represents a promising tool in modern diagnostic pathology and precision oncology, bridging morphology, molecular alterations, and therapeutic decision-making.

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Cite

BibTeXRIS
BibTeX
@article{diluvio2026beyond,
  title = {{Beyond Mesothelioma: From Diagnostic Biomarker to Therapeutic Opportunity—The Emerging Role of MTAP in Cancer}},
  author = {Anna Diluvio and Stefano Lucà and Lucia Iavarone and Valeria Masola and Alfonso Fiorelli and Floriana Morgillo and Giuseppe D’Abbronzo and Renato Franco},
  journal = {International Journal of Molecular Sciences},
  year = {2026},
  month = oct,
  doi = {10.3390/ijms27219653},
  url = {https://www.mdpi.com/1422-0067/27/21/9653},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Beyond Mesothelioma: From Diagnostic Biomarker to Therapeutic Opportunity—The Emerging Role of MTAP in Cancer
AU  - Anna Diluvio
AU  - Stefano Lucà
AU  - Lucia Iavarone
AU  - Valeria Masola
AU  - Alfonso Fiorelli
AU  - Floriana Morgillo
AU  - Giuseppe D’Abbronzo
AU  - Renato Franco
PY  - 2026
DA  - 2026/10/28
JO  - International Journal of Molecular Sciences
DO  - 10.3390/ijms27219653
UR  - https://www.mdpi.com/1422-0067/27/21/9653
AB  - Methylthioadenosine phosphorylase (MTAP) loss is an emerging biomarker in several human malignancies, mainly due to its frequent co-deletion with CDKN2A on chromosome 9p21. Beyond its diagnostic value, MTAP deficiency has important biological consequences, including metabolic reprogramming, immune microenvironment modulation, and increased dependency on PRMT5-related pathways. This review summarizes the current evidence on MTAP alterations across different tumor types. The role of MTAP immunohistochemistry as a practical surrogate for CDKN2A homozygous deletion is discussed, together with its advantages and interpretative limitations. In addition, the potential predictive relevance of MTAP loss for immunotherapy, antifolate-based treatments, and novel PRMT5-targeted strategies is explored. Overall, MTAP assessment represents a promising tool in modern diagnostic pathology and precision oncology, bridging morphology, molecular alterations, and therapeutic decision-making.
SN  - 1422-0067
ER  -