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Testicular germ cell tumor: a comprehensive review

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Abstract

Testicular tumors are the most common tumors in adolescent and young men and germ cell tumors (TGCTs) account for most of all testicular cancers. Increasing incidence of TGCTs among males provides strong motivation to understand its biological and genetic basis. Gains of chromosome arm 12p and aneuploidy are nearly universal in TGCTs, but TGCTs have low point mutation rate. It is thought that TGCTs develop from premalignant intratubular germ cell neoplasia that is believed to arise from the failure of normal maturation of gonocytes during fetal or postnatal development. Progression toward invasive TGCTs (seminoma and nonseminoma) then occurs after puberty. Both inherited genetic factors and environmental risk factors emerge as important contributors to TGCT susceptibility. Genome-wide association studies have so far identified more than 30 risk loci for TGCTs, suggesting that a polygenic model fits better with the genetic landscape of the disease. Despite high cure rates because of its particular sensitivity to platinum-based chemotherapy, exploration of mechanisms underlying the occurrence, progression, metastasis, recurrence, chemotherapeutic resistance, early diagnosis and optional clinical therapeutics without long-term side effects are urgently needed to reduce the cancer burden in this underserved age group. Herein, we present an up-to-date review on clinical challenges, origin and progression, risk factors, TGCT mouse models, serum diagnostic markers, resistance mechanisms, miRNA regulation, and database resources of TGCTs. We appeal that more attention should be paid to the basic research and clinical diagnosis and treatment of TGCTs.

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Acknowledgements

This work was supported by the Young Elite Scientists Sponsorship Program by CAST (Grant no. YESS20160118 to SR Chen); National Natural Science Foundation of China (31501198 to SR Chen); CAS-TWAS President’s Fellowship for International PhD Students (to A Batool).

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  1. Aalia Batool, Najmeh Karimi and Xiang-Nan Wu contributed equally to this review.

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  1. State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, 1 Beichen West Road, Chaoyang District, Beijing, 100101, China

    Aalia Batool, Najmeh Karimi, Xiang-Nan Wu, Su-Ren Chen & Yi-Xun Liu

  2. University of Chinese Academy of Sciences, Beijing, 100049, China

    Aalia Batool, Najmeh Karimi & Xiang-Nan Wu

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Batool, A., Karimi, N., Wu, XN. et al. Testicular germ cell tumor: a comprehensive review. Cell. Mol. Life Sci. 76, 1713–1727 (2019). https://doi.org/10.1007/s00018-019-03022-7

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