S-甲基-5'-硫腺苷磷酸化酶 (MTAP) 缺陷是非小细胞肺癌 (NSCLC) 及其他癌症的新兴生物标志物。 MTAP 基因位于染色体区域 9p21.3，这是所有人类癌症中最常见的纯合性缺失之一（9p21 缺失）。大多数胸膜间皮瘤都存在 9p21 缺失，它是一种既定的诊断标志物。直到最近，荧光原位杂交 (FISH) 仍是检测 9p21 缺失的金标准，但通过免疫组织化学 (IHC) 检测 MTAP 表达缺失作为一种易于应用且经济有效的诊断替代标记物变得越来越重要。此外，据报道 13% 的 NSCLC 中 MTAP 丢失正在成为 NSCLC 和其他癌症类型两种不同情况下的新兴预测生物标志物：1) MTAP 丢失似乎负面预测对免疫检查点抑制剂 (ICI) 治疗的反应通过肿瘤微环境的沉默，2) MTAP 损失可作为新型靶向治疗策略的预测生物标志物。 MTAP 缺乏会导致蛋白质精氨酸甲基转移酶 5 (PRMT5) 的功能受损，因为它受到 MTAP 累积底物甲硫腺苷 (MTA) 的部分抑制。这一过程使得 MTAP 缺陷的肿瘤细胞严重依赖 PRMT5 的剩余功能，使其成为合成致死的完美靶点。事实上，MTA 合作的 PRMT5 抑制剂现已在多项临床试验中进行测试，在实体恶性肿瘤方面取得了有希望的早期结果。随着 MTAP IHC 作为预测性生物标志物的出现，可能很快就会将其纳入 NSCLC 和其他肿瘤的常规诊断中。在这篇综述文章中，我们总结了有关 MTAP 在胸部肿瘤中作用的最新文献，并评估了不同的检测方法，包括 IHC、FISH 和下一代测序。版权所有 © 2024 作者。由 Elsevier B.V. 出版。保留所有权利。

S-methyl-5'-thioadenosine phosphorylase (MTAP) deficiency is an emerging biomarker in non-small cell lung cancer (NSCLC) and beyond. The MTAP gene is located in the chromosomal region 9p21.3, which shows one of the most common homozygous deletions across all human cancers (9p21 loss). Loss of 9p21 is found in the majority of pleural mesotheliomas, where it serves as an established diagnostic marker. Until recently, fluorescence in situ hybridization (FISH) was the gold standard for the detection of 9p21 losses, but loss of MTAP expression by immunohistochemistry (IHC) gains increasing importance as an easy to apply and cost-effective diagnostic surrogate marker. Besides, MTAP loss, which has been reported in 13% of NSCLC, is becoming an emerging predictive biomarker in two different scenarios in NSCLC and other cancer types: 1) MTAP loss seems to negatively predict the response to immune checkpoint inhibitor (ICI) treatment via silencing of the tumor microenvironment, and 2) MTAP loss serves as a predictive biomarker for novel targeted treatment strategies. MTAP deficiency leads to an impaired function of the protein arginine methyltransferase 5 (PRMT5) due to its partial inhibition by MTAP's accumulating substrate methylthioadenosine (MTA). This process leaves MTAP deficient tumor cells heavily dependent on the remaining function of PRMT5, making it a perfect target for synthetic lethality. Indeed, MTA-cooperative PRMT5-inhibitors are now tested in several clinical trials with promising early results in solid malignancies. With its emergence as a predictive biomarker, the implementation of MTAP IHC into diagnostic routine for NSCLC and other tumors is likely to take place soon. In this review article, we summarize the current literature on the role of MTAP in thoracic tumors and evaluate different testing methods, including IHC, FISH and next generation sequencing.Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.