Molecular Biology of Pediatric and Adult Male Germ Cell Tumors

Abstract

Cancer is a leading cause of death by disease in children and the second most prevalent of all causes in adults. Testicular germ cell tumors (TGCTs) make up 0.5% of pediatric malignancies, 14% of adolescent malignancies, and are the most common of malignancies in young adult men. Although the biology and clinical presentation of adult TGCTs share a significant overlap with those of the pediatric group, molecular evidence suggests that TGCTs in young children likely represent a distinct group compared to older adolescents and adults. The rarity of this cancer among pediatric ages is consistent with our current understanding, and few studies have analyzed and compared the molecular basis in childhood and adult cancers. Here, we review the major similarities and differences in cancer genetics, cytogenetics, epigenetics, and chemotherapy resistance between pediatric and adult TGCTs. Understanding the biological and molecular processes underlying TGCTs may help improve patient outcomes, and fuel further investigation and clinical research in childhood and adult TGCTs.

Keywords: epigenomics; genomics; germ cell tumors; pediatric and adult; testicular cancer.

Figure 1

Etiopathogenesis of testicular germ cell tumors (TGCTs). The red letters mean chromosomic loss, and the blue letters chromosomic gain. The blue arrows represent the non-GCNIS pathway and the red arrow represents the GCNIS pathway. GCNIS: germ cell neoplasia in situ; KITL: KIT ligand; TSPY: testis-specific Y-encoded protein.

Figure 2

Comparison of clinical and molecular differences between adult and pediatric patients with TGCTs as a hallmark of cancer. The letter “A” represents adults, “C” represents child, and “B” represents both adult and child. Adapted from Hanahan and Weinberg [112].