The mapping of the human genome has ushered in the age of precision cancer medicine, in which an individual’s treatment can be tailored to the specific genetic abnormalities of his or her disease.

In recent years, much attention has been brought to genetic testing for cancer risk, particularly around Angelina Jolie and her decision to undergo preventative surgeries.

Amy Kindstedt, a 9-year-old, was diagnosed with Pleuropulmonary Blastoma (PPB), a rare tumour of the lung, in 2014. PPB tumours can progress from a more benign to a more aggressive type if not detected early. Because she had a particularly aggressive form, her treatment required the removal of her left lung, radiation, and a year of chemotherapy

Knowing that PPB is often caused by mutations in a gene known as DICER1, her Dana-Farber/Boston Children’s care team tested Amy for the gene. Once they found she had a mutation in the gene, her parents, grandparents, and younger brothers Hunter and Thatcher were tested as well.

Hunter, just 19 months old, was found to have the mutation. Two days after Amy’s lung removal surgery, a CT scan revealed Hunter also had a lung tumour, felt to be PPB.

“Less than a month after Amy’s lung surgery, Hunter had a tumour removed from his lung too,” recalls mom Susan Kindstedt. “Amy was in the middle of a five-day chemotherapy course, so while my parents sat with her in the Jimmy Fund Clinic at Dana-Farber, my husband and I were next door at Boston Children’s for Hunter’s surgery.”

Because he had no other symptoms, Hunter’s tumour would likely not have been caught until much later were it not for genetic tests revealing he had the DICER1 mutation. And, because his tumour was much smaller and at an earlier stage than Amy’s, his lung was saved and no further treatment was necessary.

Amy hates cancer, but she is very thankful for one thing: Because genetic testing on her baby brother Hunter revealed he had the same genetic mutation she did, his cancer was caught much earlier – possibly sparing him the same level of intense treatment she endured.

Amy takes great pride in the knowledge that, not only did she help save her brother from pain, but that future generations of her family will now also know they should be tested for DICER1.

Sometimes, a gene that contributes to disease contains a mutation, similar to misspelling a word, which can lead to a higher risk of cancer. In Jolie’s case, this was a mutation in the BRCA1 gene.

When Noah Arnold developed tumors on his kidney around his first birthday, doctors at St. Jude Children’s Research Hospital in Memphis removed them and diagnosed them as benign. Despite that good news, a strong history of thyroid problems in Noah’s father’s family aroused his doctors’ suspicions.

Noah’s parents gave the go-ahead for a genetic test that showed the boy had a mutation in a gene called Dicer1, which is associated with a heightened risk of thyroid and other cancers. Noah’s older sister, Sarah Anne, now 6 years old, was found to have the mutation, too. Now she and her brother, who turns 3 in December, undergo regular ultrasound screening and other tests to check for early tumor formation on their kidneys and other organs.

The Arnold children may never develop cancer. But with some tumors associated with a Dicer1 mutation, says Emily Quinn, the genetics counselor on their case at St. Jude, “if we catch it early, the kids have much better outcomes than if we catch it later.”

Knowing which mutated genes are at fault for a particular cancer can also help physician-scientists determine, through genetic testing, which members of a patient’s family may have the same mutations and be at higher risk.

Looking for a genetic link to paediatric cancers reflects expanding efforts to match adult and child patients with drugs that target specific mutations found to drive the growth of their tumours. By analysing DNA not only from a diagnosed child’s tumor cells but also normal DNA from blood or skin tissue from the child and other family members, doctors can determine whether the cancer is likely to be unique to the child, or if a potentially cancer-causing mutation is lurking in the family.

The results can influence treatment and indicate whether children might be at risk for other tumors later in life, or pass on risk to future children of their own, says Kim Nichols, a pediatric oncologist who heads St. Jude’s cancer predisposition clinic in Memphis, Tenn. If the cancer arose from a parent, it “has implications that extend well beyond that child and touches upon relatives,” she says.

According to a landmark study presented in March 2017, 12% of childhood cancer survivors carry germline mutations that put them or their children at increased risk of developing cancer.

Unlocking Answers: Pediatric genetic testing at C.S. Mott Children’s Hospital

The study of more than 3,000 long-term St. Jude childhood cancer survivors is apparently the first time whole genome sequencing has been used in a large group of cancer survivors to study the impact of genetic factors on the lifetime cancer risk.

These results suggest that many more childhood cancer survivors would likely benefit from genetic screening and counseling,” said Leslie Robison, Ph.D., chair of the St. Jude Department of Epidemiology and Cancer Control. “For cancer survivors, this research marks the beginning of a new era in cancer surveillance and prevention.” He and Jinghui Zhang, Ph.D., chair of the St. Jude Department of Computational Biology, are co-senior authors.

Researchers recommended expanding genetic screening and counseling to include childhood cancer survivors who have been diagnosed with second cancers and whose pediatric cancer treatment did not include radiation therapy. Referrals are also now recommended for survivors whose initial treatment included radiation therapy and who have developed secondary breast cancer, thyroid cancer, or sarcomas at the radiation treatment sites.

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