How the FISH Technique Could Quickly Find Genetic Mutations

By Tony Wang


Chemotherapy and radiation therapy are both treatments that are often used to treat cancer; however, they are also known to cause several harsh side effects in patients. These side effects can not only harm patients, but, more worryingly, may also impact their future children. This is supported by empirically-gathered data that shows that radiation and chemotherapy treatments are “genotoxic,” which means that they can not only mutate a human’s DNA, but can also damage the chromosomes in a patients’ healthy, noncancerous cells. When this occurs in a germline cell—which are egg cells and sperm cells in women and men, respectively—it can lead to very serious fetal and birth defects in their future children.

cell lines
Image Credit: Flickr @ Andy Leppard

Currently, there are no efficient, effective, and affordable tests that can be used to track a man’s germline cell health in regards to whether or not they contain any chromosomal mutations caused by chemotherapy and/or therapy treatments. This is particularly concerning, as if a man is unaware of his germline cell health, and attempts to conceive a child, they may unknowingly pass on a defect to them. But recent evidence from a study led by Andrew Wyrobek at the Lawrence Livermore National Laboratory suggests that this may soon change. According to Wyrobek, a new test that can quickly and easily identify when a sperm cell is carrying chromosomal mutations could soon be released to the public. In a paper published in the journal PLOS One, the international team reported their success in adapting an established cellular DNA analysis technique called fluorescence in situ hybridization (FISH) to probe sperm DNA. This version of the FISH technique, known as the AM8 sperm FISH protocol, has been in the works by the research team for several decades. This method can detect balanced chromosomal abnormalities, which are genetic rearrangements with no loss or gain of genetic material. These balanced rearrangements are compatible with live birth and heritable to future pregnancies, and affected children are likely to experience reduced fertility when they want to have children of their own.

The research team evaluated the AM8 FISH approach on sperm from nine Hodgkin lymphoma patients, who provided samples before, during, and after a multidrug treatment regimen and radiation therapy. Results from the FISH protocol tests were astonishingly accurate, indicating that sperm produced during the Hodgkin lymphoma treatment had ten times more chromosomal defects compared with sperm produced prior to treatment.