Genetics of testicular germ cell tumors. Issue 4 (July 2019)

• Record Type: Journal Article
• Authors: Singla, Nirmish; Lafin, John T.; Ghandour, Rashed A.; Kaffenberger, Samuel; Amatruda, James F.; Bagrodia, Aditya
• Is Part Of: Current opinion in urology. Volume 29:Issue 4(2019:Jul.)
• Publication Date: 2019-07
• Subjects: chemoresistance -- genetics -- germ cell tumor -- inheritance -- testis cancer; Urology -- Periodicals; Review Literature -- Bibliography; Review Literature -- Periodicals; Male Urogenital Diseases -- Bibliography; Male Urogenital Diseases -- Periodicals; Female Urogenital Diseases -- Bibliography; Female Urogenital Diseases -- Periodicals; Urologic Diseases -- Bibliography; Urologic Diseases -- Periodicals; Periodicals; 616.6005
• DOI: 10.1097/MOU.0000000000000642
• Languages: English
• ISSNs: 1473-6586

Abstract

Abstract : Purpose of review: Understanding the molecular basis underlying testicular germ cell tumors (TGCTs) may help improve patient outcomes, particularly for patients with poorer risk or chemoresistant disease. Here, we review the major contemporary advances in elucidating TGCT genetics by discussing patterns of TGCT inheritance, recent genomic and transcriptomic discoveries in TGCT, and the role of genetics in predicting therapeutic resistance and in guiding treatment. Recent findings: In the absence of a major high-penetrance TGCT susceptibility gene, inheritance is likely driven by a complex polygenic model with considerable variation. The most common genomic alterations found in TGCTs include gains in chromosome 12p and mutations in KIT, KRAS, and NRAS, particularly in seminomas. Sensitivity to cisplatin-based chemotherapy likely relies on intact TP53, reciprocal loss of heterozygosity, and high mitochondrial priming. Targetable mutations are uncommon in TGCTs, however, posing a challenge for the development of effective personalized therapies. Consistent with the characteristically low tumor mutational burden, immune checkpoint inhibitors do not appear to be effective for most TGCTs. Summary: Refinements in next-generation sequencing techniques over the last few years have enabled considerable advances in elucidating the genomic, transcriptomic, and epigenetic landscape of TGCTs. Future efforts focused on developing novel treatment modalities are needed.