- Testicular cancers originate from germ cells.
- Most germ cell tumors are highly curable due to sensitivity to chemotherapy.
- These tumors exhibit certain changes at genomic levels which explains the high susceptibility of testicular cancers to chemotherapy.
Certain genomic changes that maybe unique and integral to testicular cancer development have been identified.
The research was led by scientists at Dana-Farber Cancer Institute and the findings were published in Nature
‘The unique genomic ‘signatures’ that drive the testicular germ cell tumors explains why the great majority are highly curable with chemotherapy.’
This may explain why testicular cancer is highly curable with chemotherapy and the factors in other solid tumors that render them resistant to chemotherapy.
Cancers of the testes are known as germ cell tumors. The germ cells produce sperm and eggs.
In 2016, about 8,720 new cases are expected in the U.S., with about 380 deaths.
Although they are rare, primary testicular germ cell tumors are the most common solid cancers in young men.
More than 80% of patients with germ cell tumors are cured, even after metastasis of cancer because these tumors are highly sensitive to chemotherapy.
About 10% of patients with metastatic germ cell tumors die because some of the cells develop resistance to chemotherapy.
Previous genomes studies of testicular tumors have revealed mutations and chromosome damage, but have failed to identify alterations or events associated with chemosensitivity or resistance.
The new research was carried out by scientists led by Eliezer Van Allen, MD, of Dana-Farber and the Broad Institute of MIT and Harvard, and Christopher Sweeney, MBBS, of Dana-Farber.
For the study, the scientists analyzed samples of 59 tumors from 49 patients treated between 1997 and 2014 at Dana-Farber/Brigham and Women's Cancer Center (DF/BWCC) over a period.
The samples were studied with whole-exome DNA sequencing and RNA transcriptome analysis, and the findings were correlated with clinical outcomes data.
"Although mutated genes are the main drivers of many cancers, we didn't find any one gene that really explains the formation of testicular cancers." Sweeny said.
Reasons for Chemo-Sensitivity of Testicular Cancer-
- Gain and loss of alleles
- Presence of intact copies p53 genes
- Tumor cells undergo apoptosis
Chromosomes carry two versions of DNA called as alleles, one from each parent.
Researchers reported a type of chromosomal damage called reciprocal loss of heterozygosity (RLOH) in testicular germ cell tumors.
In this type of damage, multiple parts of the genome showed a gain of one parental allele while simultaneously losing a copy of the other parental allele.
The hallmark feature of this study was the identification of gain and loss of DNA copies that makes the chromosomes profoundly deranged.
This must be one reason why the germ cell tumors are sensitive to chemotherapy.
The analysis also revealed that the germ cell tumors that showed sensitivity to chemotherapy possessed intact copies of the p53 gene.
This gene directs cells to make a tumor-suppressor protein that prevents the cells from forming tumors.
Many other cancers contain mutated or lost p53 genes, indicating they have lost this protective factor.
Another reason why testicular cancers are curable is because most cells involved in this cancer undergo self-destruction through apoptosis.
Apoptosis, is the process programmed cell death, by which the body gets rid of unneeded and dangerously abnormal cells.
Whereas most other forms of cancers have evolved strategies to block the cell's orders to self-destruct.
This makes most of the testicular tumors highly susceptible to chemotherapy because their cells are already highly "primed" for apoptotic death.
"The new study, gives us insights into germ cell tumor biology that haven't been found to this degree and provide a strong base to explore these very interesting findings further." Sweeney said.
Intensive study on germ cell tumors is absent due to its rarity and due to limited research funding research funding is more scarce.