A systematic literature review of MTAP deletions in solid and hematologic Cancers

Background: Methylthioadenosine phosphorylase (MTAP) deficiency is observed across multiple cancers and represents an emerging biomarker with therapeutic potential via synthetic lethality with PRMT5 inhibition. This systematic literature review summarizes the prevalence of MTAP deletions or loss of...

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Main Authors: Mary C. Clouser, Mina Suh, Naimisha Movva, Janet S. Hildebrand, Susan T. Pastula, Martina Schoehl, Antreas Hindoyan, Akhila Balasubramanian, Jon P. Fryzek, Soo-Ryum Yang
Format: Article
Language:English
Published: Elsevier 2025-01-01
Series:Cancer Treatment and Research Communications
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Online Access:http://www.sciencedirect.com/science/article/pii/S2468294225001029
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author Mary C. Clouser
Mina Suh
Naimisha Movva
Janet S. Hildebrand
Susan T. Pastula
Martina Schoehl
Antreas Hindoyan
Akhila Balasubramanian
Jon P. Fryzek
Soo-Ryum Yang
author_facet Mary C. Clouser
Mina Suh
Naimisha Movva
Janet S. Hildebrand
Susan T. Pastula
Martina Schoehl
Antreas Hindoyan
Akhila Balasubramanian
Jon P. Fryzek
Soo-Ryum Yang
author_sort Mary C. Clouser
collection DOAJ
description Background: Methylthioadenosine phosphorylase (MTAP) deficiency is observed across multiple cancers and represents an emerging biomarker with therapeutic potential via synthetic lethality with PRMT5 inhibition. This systematic literature review summarizes the prevalence of MTAP deletions or loss of expression and prognostic impacts of MTAP deletions or loss in adult and pediatric patients with specific solid or hematologic cancers. Methods: Following PRISMA methodology, the literature on MTAP deletion or loss in multiple cancer types was reviewed. Prevalence, laboratory testing methods, patient characteristics, and clinical outcomes according to MTAP status were synthesized. Study quality was determined using standard tools. Results: Of the 352 identified studies, 37 reported on MTAP. The majority were retrospective cohorts (N=32; 86%). The most common laboratory test type was NGS, specifically FoundationOne (N=7, 24%). MTAP deletion (loss) prevalence varied across tumor types and were generally lowest in gastric cancer (4%–14%) and highest in glioblastoma (26%–60%). MTAP deletion was correlated with higher prevalence of KRAS. Variation by age, gender, and race/ethnicity were inconsistently reported. Survival outcomes were reported most often for GBM and NSCLC with some studies suggesting worse overall survival among patients with MTAP deletions, although the evidence was heterogeneous. Conclusion: This is the first systematic review to summarize the literature on MTAP deletions or loss of expression across several solid and hematologic cancers. MTAP deletions and/or loss of expression occur in many cancer types, presenting a promising target for pan-cancer therapy.
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spelling doaj-art-ede2a30de3bf48efbdbbd18499759d242025-08-20T03:58:41ZengElsevierCancer Treatment and Research Communications2468-29422025-01-014410096610.1016/j.ctarc.2025.100966A systematic literature review of MTAP deletions in solid and hematologic CancersMary C. Clouser0Mina Suh1Naimisha Movva2Janet S. Hildebrand3Susan T. Pastula4Martina Schoehl5Antreas Hindoyan6Akhila Balasubramanian7Jon P. Fryzek8Soo-Ryum Yang9Amgen, Thousand Oaks, CA, USA; Corresponding author at: One Amgen Center Drive, Mail Stop: 38-4-B, Thousand Oaks, CA 91320-1799.EpidStrategies, A Division of ToxStrategies, LLC, Mission Viejo, CA, USAEpidStrategies, A Division of ToxStrategies, LLC, Mission Viejo, CA, USAAmgen, Thousand Oaks, CA, USAEpidStrategies, A Division of ToxStrategies, LLC, Mission Viejo, CA, USAAmgen, Thousand Oaks, CA, USAAmgen, Thousand Oaks, CA, USAAmgen, Thousand Oaks, CA, USAEmployee of EpidStrategies at the time of study conduct, USAMemorial Sloan Kettering Cancer Center, New York, NY, USABackground: Methylthioadenosine phosphorylase (MTAP) deficiency is observed across multiple cancers and represents an emerging biomarker with therapeutic potential via synthetic lethality with PRMT5 inhibition. This systematic literature review summarizes the prevalence of MTAP deletions or loss of expression and prognostic impacts of MTAP deletions or loss in adult and pediatric patients with specific solid or hematologic cancers. Methods: Following PRISMA methodology, the literature on MTAP deletion or loss in multiple cancer types was reviewed. Prevalence, laboratory testing methods, patient characteristics, and clinical outcomes according to MTAP status were synthesized. Study quality was determined using standard tools. Results: Of the 352 identified studies, 37 reported on MTAP. The majority were retrospective cohorts (N=32; 86%). The most common laboratory test type was NGS, specifically FoundationOne (N=7, 24%). MTAP deletion (loss) prevalence varied across tumor types and were generally lowest in gastric cancer (4%–14%) and highest in glioblastoma (26%–60%). MTAP deletion was correlated with higher prevalence of KRAS. Variation by age, gender, and race/ethnicity were inconsistently reported. Survival outcomes were reported most often for GBM and NSCLC with some studies suggesting worse overall survival among patients with MTAP deletions, although the evidence was heterogeneous. Conclusion: This is the first systematic review to summarize the literature on MTAP deletions or loss of expression across several solid and hematologic cancers. MTAP deletions and/or loss of expression occur in many cancer types, presenting a promising target for pan-cancer therapy.http://www.sciencedirect.com/science/article/pii/S2468294225001029CancerCDKN2ACo-mutationsHomozygous deletionsMTAPSurvival
spellingShingle Mary C. Clouser
Mina Suh
Naimisha Movva
Janet S. Hildebrand
Susan T. Pastula
Martina Schoehl
Antreas Hindoyan
Akhila Balasubramanian
Jon P. Fryzek
Soo-Ryum Yang
A systematic literature review of MTAP deletions in solid and hematologic Cancers
Cancer Treatment and Research Communications
Cancer
CDKN2A
Co-mutations
Homozygous deletions
MTAP
Survival
title A systematic literature review of MTAP deletions in solid and hematologic Cancers
title_full A systematic literature review of MTAP deletions in solid and hematologic Cancers
title_fullStr A systematic literature review of MTAP deletions in solid and hematologic Cancers
title_full_unstemmed A systematic literature review of MTAP deletions in solid and hematologic Cancers
title_short A systematic literature review of MTAP deletions in solid and hematologic Cancers
title_sort systematic literature review of mtap deletions in solid and hematologic cancers
topic Cancer
CDKN2A
Co-mutations
Homozygous deletions
MTAP
Survival
url http://www.sciencedirect.com/science/article/pii/S2468294225001029
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