Study describes reasons for testing pediatric cancer patients for inherited genes

Because childhood cancers are rare, many details about their biology remain unknown. In the field of cancer genetics, there is limited understanding of how inherited genetic changes can contribute to the formation and growth of tumors. Establishing links between particular genetic mutations and disease requires extensive data, which until recently were largely unavailable for pediatric cancers.

Now tests like MSK-IMPACT^TM can screen tumors for mutations in over 500 genes as well as analyze normal (germ) cells in patients. In the largest study of its kind to date, researchers from Memorial Sloan Kettering’s pediatric program, MSK Kids, report details of germline genomic sequencing for 751 pediatric patients treated for solid tumors.

The article, published on February 15, 2021, in Nature Cancer, explains how understanding the hereditary factors associated with childhood cancer can help patients and their families better understand the risk of future cancers. Armed with this information, they can undergo screening and prevention measures if necessary. It can also be used for family planning purposes. In a small but growing number of cases, this information can even help select the most appropriate treatment for a child’s cancer.

Many of the associations we learn from these types of tests were not previously known and have broadened our understanding of how inherited genes may be linked to a predisposition to pediatric cancers. We hope to raise awareness of these connections and how testing for these inherited genes could be clinically useful. “

Elise Fiala, first author of the article, genetic counselor

Updated guidelines for genetic testing

For certain types of adult cancers – such as breast cancers and colorectal cancers diagnosed in young adults – the importance of screening patients for mutations BRCA1 and BRCA2 genes and Lynch syndrome are well established, especially for people who may have a family history of many cancers. But the hereditary links with pediatric cancers have been largely unrecognized. In addition, the guidelines for which pediatric patients should be screened for hereditary mutations are based on limited data.

“This study shows that the criteria we are currently using to determine who should receive germline tests are imperfect,” says physician-scientist Michael Walsh, lead author of the article, who leads research on the hereditary genomics of pediatric cancer at the Robert and Kate Niehaus Center for Inherited at MSK. Cancer genomics.

“In about half of the patients in whom we found a hereditary predisposition, we would not have predicted the detection of a cancer predisposing mutation and would not have screened them,” he adds. These results included mutations in the BRCA the genes; genes associated with Lynch syndrome; the gene TP53, which is linked to an inherited disorder called Li-Fraumeni syndrome; and others.

The value of genetic testing

There are many reasons why it is important to know if a child’s cancer is caused by an inherited genetic mutation, which are described in the article.

On the one hand, it can guide the treatment. For example, tumors caused by genes associated with Lynch syndrome can potentially respond to immunotherapy drugs called checkpoint inhibitors. These drugs usually don’t work in pediatric cancers, so unless a patient is known to have Lynch syndrome, they likely won’t be considered.

Learning that a child has an inherited cancer gene can also help families. Parents, siblings, and other family members may benefit from genetic testing to look for the same genetic mutation. If the results are positive, they may be monitored more closely for cancer or consider preventative measures. For families who plan to have more children, in vitro fertilization and preimplantation diagnosis – in which embryos are tested for harmful mutations before they are put into the uterus – may be considered.

Screening for germline mutations in pediatric cancers can also help researchers learn more about the causes of some of these cancers, which could lead to new methods of diagnosis and treatment. In the Nature Cancer paper, researchers provide evidence of a previously unrecognized link between a gene called CDKN2A and osteosarcoma, the most common form of bone cancer in children and young adults.

Expanding the reach of childhood cancer survivors

Researchers report that only 31% of families with children who inherited mutations chose to look for genetic tests in other parents. Ms Fiala said it was not surprising because these families were dealing with a child being treated for cancer.

“But these findings have much broader implications than for the 16,000 children diagnosed with cancer in the United States each year,” says Dr Walsh.

Ms Fiala says the study’s findings are important not only for children currently being treated for cancer and their families, but also for cancer survivors. “A lot of people who were treated for cancer as children are now the age they plan to have children,” she says. “We would love to see people who have a history of cancer and now plan families to consider getting tested so they can learn more about their risks and options.