Article
Genomic Changes Ensure Chemotherapy Response in Testicular Cancer
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Research from the Dana-Farber Cancer Institute and the Broad Institute, published in Nature, has identified genomic changes that could explain the development of testicular cancer and why this disease is more responsive to chemotherapy.
Cancer of the testis is characterized by germline changes, and although it is a rare disease in the overall population, primary testicular germ cell tumors are common in young men. However, these tumors are curable with chemotherapy. Now, research from the Dana-Farber Cancer Institute and the Broad Institute, published in Nature, has identified genomic changes that could explain the development of testicular cancer, and why this disease is more responsive to chemotherapy.
More than 80% of patients with germ-cell tumors are cured, even if their cancer has metastasized; however, chemotherapy resistance could result in 10% of patient deaths.
For their study, scientists used whole-genome and transcriptome sequencing of precursor, primary, and chemoresistant metastatic human germ-cell tumors and found that the primary somatic features of these tumors are highly recurrent chromosomal amplifications and reciprocal deletions. These, the authors found, were much more enriched in germ-cell tumors than in the 19 other cancer types that they were compared against. Another characteristic germline mutation observed in the testicular tumors was the reciprocal loss of heterozygosity (RLOH), wherein multiple parts of the genome gain 1 parental allele and simultaneously lose a copy of the other parental allele. This RLOH in the tumors is associated with a loss of 2 pluripotency markers, NANOG and POU5F1, in chemoresistant teratomas.
Eliezer Van Allen, MD, senior author on the study, believes that the RLOH may be responsible for the development of germ cell tumors that are also sensitive to chemotherapy. The mechanism of how this happens remains to be discovered.
Co-author Christopher Sweeney, MBBS, stated that because of the rarity of these tumors, funding is scarce and not much information is known. He thinks that their results published in Nature provide additional insight into germ cell tumor biology and create reason for further exploring these tumor types.
