Genetic mutations linked to cancer inherited by 1 in 12 childhood cancer patients

A study found one in twelve childhood cancer patients had inherited genetic mutations from their parents which predispose them to developing cancer. Analyzing 565 genes linked to increased cancer risk, researchers found 8.5% of patients had inherited mutations compared to 1.1% of normal individuals from the 1000 Genomes project. More than half of the patients with inherited mutations did not have a family history of cancer, and the authors of the study in the New England Journal of Medicine suggest their findings make a case for genomic screening of all pediatric cancer patients, and the families of patients with inherited mutations.


Dr. Jaime E. Vengoechea, Assistant Professor, Department of Human Genetics, Division of Medical Genetics, Emory University (webpage):

Expertise: clinical genetics for adults, including inherited cancer syndromes, cardiovascular disorders and hereditary neurologic disorders.

“This study is a great example of the importance of genetic testing in modern medicine. The children that were part of this research had a genetic test that looked for inherited mutations, specifically in genes that are known to cause hereditary cancer. The researchers found that 8.5% of children with cancer were born with a genetic change that increases the lifetime risk of cancer. In comparison, they found the prevalence of these mutations in the general population was only 1%. In medical genetics, we believe that in “extreme” examples of a disease, we are more likely to find a genetic cause. One way to understand these findings is to look at childhood cancer as an “extreme” form of cancer; similar to adults with very early heart disease or hereditary forms of diabetes. In these cases, we can find genetic changes that impact the healthcare of the patient and their family.

“The study has implications for the healthcare not only of the children, but also their parents, siblings and other relatives. Two examples: the most common mutation was found in the TP53 gene which is known to significantly increase the lifetime risk of developing all sorts of cancers, and currently we recommend that they undergo extra screening and avoid unnecessary radiation (for example avoiding CT scans as much as possible). Another commonly mutated gene was BRCA2, which causes hereditary breast and ovarian cancer. Women with BRCA2 mutations should start breast cancer screening earlier, and many consider the option of having breast surgery before cancer occurs.

“The children with identified mutations should undergo special screening. Their relatives need to be tested to see if they have the mutation and, if they do, they should also have the additional screening. Of note, insurance companies often initially refuse to pay for this kind of genetic testing. However, this paper shows the importance of genetic testing in childhood cancer. The next challenge for clinical geneticists is to agree upon a list of high-impact genes that should be checked in every case of childhood cancer, as some genes have very small effects. By getting a “cleaner” list of genes, we can implement genomic screening for all cases of childhood cancer and better justify to insurance companies why these need to be checked.”


Beth N. Peshkin, Professor of Oncology and Senior Genetic Counselor, Georgetown Lombardi Comprehensive Cancer Center, Georgetown University (webpage): 

Expertise: Cancer genetic counseling and testing, patient education, and decision-making. Behavioral outcomes and medical decision-making, ethical issues in genetic counseling and testing.

“This study provides important insights about genomic testing in pediatric oncology patients.

“Though it is hoped that identifying mutations in oncology patients will lead to tailored treatments, it’s likely that for many of the study participants, treatment or prognosis will not be altered by the germline findings. However, for the relatives of children with mutations in genes such as TP53, BRCA1/2, and PMS2, it is important to determine if the mutations were inherited, and if so, that at-risk relatives are notified and counseled appropriately. For example, adult female relatives of a child with a TP53 mutation may not be aware that if they too carry the mutation, their cancer risks approach 100%, with much of that risk related to breast cancer. Thus, they need to be aware of guidelines addressing surveillance and risk reduction options. Women with BRCA1/2 mutations should be informed about the unequivocal recommendation for surgical removal of both ovaries and fallopian tubes by age 35-40 to reduce mortality from ovarian, and possibly breast, cancer. Ovarian cancer is not present in most families with BRCA1/2 mutations, so this elevated risk would not be apparent but for knowledge about the familial mutation. And finally, PMS2 carriers need to know about the recommendation for early and frequent colonoscopy, beginning at age 25-30.

“The study also raises questions about whether BRCA1/2 mutations are associated with increased risks of childhood cancers. If this association is confirmed, these data may alter recommendations about testing minor children, and may affect prospective parents’ views on pre-implantation genetic diagnosis.

“Relatedly, part of the argument in favor of population screening for BRCA1/2 mutations is that offering testing based only on family history could miss as many as 50% of carriers. Zhang and colleagues found that only 40% of the children with cancer-predisposing mutations had a family history of cancer, suggesting family history is an imperfect indicator of hereditary risk. To realize the public health benefit of genetic testing for high-risk mutations, it is imperative that at-risk relatives are informed about their risk of testing positive, and the potential, sometimes lifesaving, benefits of testing , early detection, and risk reduction measures.”


Declared interests (see GENeS register of interests policy):

No interests declared.



Germline Mutations in Predisposition Genes in Pediatric Cancer‘ by Jinghui Zhang et al., published in the New England Journal of Medicine on Wednesday 18 November at 5.00PM ET which is also when the embargo will lift.



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