I remember sitting in the doctor’s office with my mom, feeling tired and legs covered in bruises. At the time, I am 12 years old, looking forward to gymnastics practice and my upcoming family vacation to Florida. I think nothing is wrong and that I am just tired from training, but I know that I would not be at the doctor if my symptoms are purely due to exhaustion.

My doctor walks into the room, does a routine check, and calls for a nurse. He turns to me and says:

“We need to test for leukemia.”

My heart drops. I know what leukemia is. I know that it took the life of a family friend when she was young. I also know that my mom’s cousin had leukemia as a child and that he survived. I know that it is cancer.

The doctors take my blood and send me home. I wait, thinking about what my life will look like if this test comes back positive. I do not know much about chemotherapy except that it makes you sick and you lose your hair. My mom is nervous, but tells me it will be fine – that I will be fine. The phone rings and my mom answers to find out if I need to head to the hospital.

“Emily is just anemic. She needs iron supplements and more red meat in her diet, but she is going to be fine.”

Relief is all I feel. I am one of the lucky ones. I do not have cancer, and my diagnosis can be treated with vitamins and burgers. Others, though, are not as lucky.


The Impact of Childhood Cancer

Every year, approximately 400,000 children are diagnosed with cancer around the world, the most common forms being leukemia, brain cancer, lymphoma and solid tumors. Despite a survival rate of 85 percent, cancer is the second leading cause of death in children ages 1 to 14.

The majority of cancers in children, like in adults, develop due to mutations in genes that lead to uncontrolled cell growth, eventually developing into cancer. In adults, these mutations can be caused by aging or long-term exposure to cancer-causing substances. Even with the high number of diagnoses each year, the origin of these genetic mutations in children is generally unknown.

Following my personal scare, I wondered why it was not me, why my body chose not to form the mutation that would ultimately lead to a cancer diagnosis. At the time, there was not a large library of information on the origin of pediatric cancer, but recent breakthroughs in genomic technology and whole exome sequencing are changing the way people view the development of cancer, as well as provide more answers to the question over 400,000 children each year want the answer to: “Why me?”


Germline Genetic Testing

Through the incorporation of germline genetic testing and genotyping, researchers are working to pinpoint other genetic causes of childhood cancer. The term “germline” refers to the genetic material passed down from a child’s parents, and through the analysis of a child’s germline genetic information, medical professionals are able to identify potential genetic risks for developing certain types of cancer.

According to the National Cancer Institute, between 6 and 8 percent of all cancers in children are caused by an inherited pathogenic variant in a cancer predisposition gene, with percentages varying across different types of cancer. Recent genomic advancements have also shown that children who inherit variants related to specific familial syndromes, such as L-Fraumeni syndrome, Fanconi anemia and Hippel-Lindau syndrome, are more likely to develop cancer in childhood.

The use of germline genetic testing and whole exome sequencing in regard to childhood cancer creates many possibilities in both prevention and treatment. The knowledge allows personalized medical treatment for individuals, as well as improves the selection of donors and the choice of time for transplantation. By identifying specific genetic mutations that are associated with childhood cancers, doctors are able to begin treatment sooner, leading to a stronger chance of survival, as well as provide more insight on making decision treatments.



Pediatric Cancers and Genomic Studies

Many pediatric cancer diagnoses are characterized by variants at the level of genes that code for epigenetic proteins, leading to the regulation of gene expressions. In the past decade, these epigenetic proteins have undergone multiple genomics-based studies, such as epigenomics and genomic sequencing, to help determine causes of both pediatric and adult cancers.

Included in these studies was the testing of the Wilms’ tumor, the most common form of pediatric kidney cancer. The studies revealed that the majority of Wilms’ tumors with AMER1 (APC Membrane Recruitment Protein 1) alterations also have epigenetic abnormalities. Almost 3 percent of pediatric Wilms’ diagnoses are due to epigenetic or genetic germline changes at the growth regulatory locus 11p15.5 without any clinical manifestation of an overgrowth. It was found that children with these germline changes have a higher percentage of familial or bilateral Wilms’ tumors.

In addition to the studies surrounding the Wilms’ tumor, multiple studies were conducted on proteins involved in epigenetic regulation, including the SWI/SNF complex. The SWI/SNF complex plays a role in chromatin remodeling, the rearrangement of chromatin from a condensed state to a transcriptionally accessible state. This allows for transcription factors and other DNA-binding proteins to access DNA and control the gene expression. The studies found that alterations of the genes encoding this complex lead to the development of non-functioning proteins, including those found to be linked to synovial sarcoma, medulloblastoma, and kidney cancer.


Acute Lymphoblastic Leukemia and Genetic History

Acute Lymphoblastic Leukemia (ALL) is the most common form of cancer in individuals under the age of 15. Recently, investigators from St. Jude Children’s Research Hospital, Singapore’s National University Health System, and other research centers have discovered that genetic ancestry-related differences in tumor subtypes possibly contribute to disparities in pediatric acute lymphoblastic leukemia outcomes, according to GenomeWeb.

The researchers used RNA sequencing, along with other genomic data, to define specific molecular features found in tumor samples from over 2,300 children around the world suffering from ALL over the course of two decades. The findings identified 21 ALL subtypes in children with European, African, South Asian, East Asian, and Native American ancestry, eight of the subtypes showing an apparent relationship to the child’s genetic ancestry.

In children with Native American ancestry, tumors with TCF3-PBX1 fusions and rearrangements affecting the CRLF2 gene were more common, while children with East Asian Ancestry were more prone to tumors containing DUX4 gene alterations and rearrangements involving ZNF384. Children with African ancestry were less likely to develop a tumor marked by hyperdiploidy and DUX4 rearrangements, but were found to be more likely to develop a tumor with fusions involving the TCF3 and PBX1 genes.



Although there have been breakthroughs in the genomics field regarding the origin of pediatric cancers, there is still a lot of work to be done to provide a firm reasoning behind a diagnosis. With bioinformatic tools such as Almaden’s g.nome®, bioinformaticians and researchers are able to accelerate discovery by eliminating the need for setting up compute infrastructure, and spending more time on what they do best: focusing on the science and helping treat or prevent pediatric cancers.


About the Author

Emily Stone is the Marketing Communications Manager for Catalyze Dallas and Almaden Genomics. She lives in Texas and is getting married to her fiancé Tyler in April 2023. She loves to cook and to be outside with the black Labrador retriever, Sadie. Click to learn more about Almaden Genomics and the g.nome platform.