Pediatric Cancers Exam 1

What is the key difference in the origin of pediatric cancers compared to adult cancers?

Pediatric cancers often originate during early development, while adult cancers typically result from accumulated genetic damage over time

Pediatric cancers typically have _____ overall mutations compared to adult cancers.

fewer

What type of genetic changes are more often drivers of pediatric cancers compared to adult cancers?

Specific mutations or structural changes in DNA that modify the epigenome

What biological process is frequently hijacked by pediatric cancer cells to drive tumor growth?

Normal developmental pathways

What is the term for the entirety of a person’s DNA?

The genome

In human cells, DNA is packaged with proteins called histones into structures known as____.

Chromatin

According to Sidebar 3, what cellular process drives unrestricted growth in pediatric cancers?

Signals that control normal development being expressed at the wrong time

How does the mechanism for evading cell death typically differ between pediatric and adult cancers?

Pediatric cancers often activate embryonic survival pathways, while adult cancers often inactivate pathways that direct cell death

Germline mutations

Genetic alterations present in egg or sperm cells, typically found in every cell of the body and can be inherited or arise de novo

Somatic Mutations

Genetic alterations acquired during a person’s lifetime that are restricted to selected cells, such as those that give rise to tumors

What are pathogenic mutations?

Changes in DNA sequence that disrupt normal cellular functions, leading to cancer

A ____ germline mutations arises for the first time in an egg or sperm cell or in the fertilized egg itself, and is not inherited from either parent.

de novo

What is the classification for a genetic variant where there is not enough information to support its role as benign or pathogenic?

Variant of Unknown Significance (VUS)

Large-scale sequencing studies have found that over what percentage of childhood tumors have diagnostic or actionable genetic alterations?

Over 70%

Up to what percentage of pediatric cancer patients have an inherited germline variant predisposing them to cancer?

Up to 18%

Cancer Predisposition Syndrome (CPS)

A recognizable pattern of cancer within families that stems from pathogenic germline variants in cancer predisposition genes

Pathogenic germline variants in the _____ gene are associated with Li-Fraumeni syndrome.

TP53

Neurofibromatosis type 1 is a cancer predisposition syndrome associated with pathogenic variants in which gene?

NF1

What genetic condition, caused by an extra copy of chromosome 21, is associated with a rare subtype of acute myeloid leukemia with better outcomes?

Down syndrome

What are germline structural variants?

Large genomic rearrangements involving 50 or more nucleotides that can increase the risk of developing pediatric solid tumors

The _____ hypothesis suggests that some malignancies develop only after a second pathogenic mutation is acquired in the remaining healthy copy of a gene that already has a germline mutation.

two-hit

What type of large structural variants, such as chromosomal rearrangements, represent a distinct category of genomic alterations that drive pediatric tumor development?

Large structural variants (SVs)

Fusion oncoprotein

A unique protein with altered function created when 2 different genes fuses, which acts as a potent cancer driver

Amplification and overexpression of which gene is an indicator of high-risk disease in neuroblastoma?

The MYCN gene

What is chromothripsis?

A complex genomic rearrangement where a chromosome shatters and is pierced back together in the wrong order

What is the primary function of epigenetic modifications?

To regulate how genes are expressed without altering the underlying DNA sequence

What type of epigenetic profiling has been established as an important diagnostic tool for pediatric brain tumors?

DNA methylation profiling

The FDA-approved therapeutic revumenib disrupts the binding of a protein encoded by the ____ gene, which plays a role in epigenetic regulation.

KMT2A

In diffuse midline gliomas (DMGs), the H3K27M mutation locks cells in what kind of state that fuels cancer growth?

An immature, proliferative state

Which developmental pathway, responsible for controlling cell fate, is aberrantly activated in hepatoblastoma, medulloblastoma and Wilms tumors?

The WNT/beta-catenin pathway

Dysregulated signaling in the ____ pathway keeps cells in an immature state and promotes survival of malignant cells in T-ALL and certain sarcomas

NOTCH

What is the tumor microenvironment (TME)?

The complex environment surrounding cancer cells, composed of supportive cells, blood vessels, signaling molecules and structural components

What is the tumor immune microenvironment (TIME)?

The network of immune cells and immune-modulating factors that interact with a tumor

What is the primary benefit of whole-genome sequencing (WGS) in pediatric cancer research?

It reveals both common and rare variants across the entire genome, providing a comprehensive view of alterations

How does single-cell analysis advance pediatric cancer research?

It captured differences between individual cells within a tumor, revealing tumor heterogeneity and detecting cell-specific signals

What type of ‘omics’ provides context on how cancer and immune cells are positioned in a tissue and how they interact?

Spatial omics

What is the term for integrated data from multiple ‘omic’ measures of a biological sample?

Multi-omics

The gene editing tool _____ allows researchers to precisely modify DNA to understand how specific genetic changes drive disease.

CRISPR

Organoids

Mini organ-like structures grown from a patient’s own cells in a 3D system that can model tumor biology and treatment response

What is a patient-derived xenograft (PDX)?

A research model created by transplanting a patient’s tumor into an immunodeficient mouse to preserve its genetic and cellular diversity

What is a genetically engineered mouse model (GEMM)?

A mouse model in which specific genes are intentionally altered to mimic cancer-driving variants to study tumor development

In diagnostics, deep learning (DL) models applied to MRI scans of children with gliomas have predicted tumor recurrence up to how far in advance?

Up to one year

What is a liquid biopsy?

A minimally invasive test that analyzes cancer-derived material, such as circulating tumor DNA (ctDNA), in body fluids like blood or urine

For central nervous system (CNS) tumors, liquid biopsy of ____ is especially promising for monitoring the disease.

Cerebrospinal fluid (CSF)

What is the primary goal of the NCI Childhood Cancer Data Initiative (CCDI)?

To gather data from every child and AYA with cancer and build an integrated data network to improve outcomes

The ____ initiative, a part of CCDI provides comprehensive clinical molecular characterization for children and AYAs with newly diagnosed solid tumors.

Molecular Characterization Initiative (MCI)

What was the key finding of the NCI TARGET program regarding the Philadelphia chromosome-like subtype of ALL?

It found many patients harbored activated signaling driven by fusions, leading to improved outcomes with tyrosine kinase inhibitors

What was the name of the precision medicine clinical trial that screened young patients for actionable genetic alterations and assigned them to matched targeted therapies?

NCI-COG Pediatric Molecular Analysis for Therapy Choice (Pediatric MATCH)

The 5-year survival for all pediatric cancers combined has increased from 63% in the mid-1970s to what percentage in 2015-2021?

87%

What percentage of pediatric cancer survivors develop one or more chronic, treatment-related health conditions?

Between 60% and more than 90%

In the US, what are the five most common cancers in children (0-14 years)?

Leukemias, CNS tumors, lymphoma, neuroblastoma and soft tissue sarcomas

In the US, what are the five most common cancers in adolescents (15-19 years)?

Lymphomas, Leukemias, germ cell and gonadal tumors, thyroid carcinoma and CNA tumors

The mortality rate for which common pediatric cancer declined by an average of 3.3% per year between 2000 and 2020?

Acute lymphoblastic leukemia (ALL)

What practice, which detects a very small number of cancer cells in the body, now guides treatment intensity for ALL?

Minimal residual disease (MRD) monitoring

The Children’s Oncology Group (COG) emerged from the merger of which four collaborative clinical trial groups?

CCG, POG, NWTSG and IRSG

In what year was the Children’s Oncology Group (COG) formed?

2000

Survival rates for adolescents and young adults (AYAS are notably ____ compared to children diagnosed with the same cancers.

lower

Pediatric cancers are classified primarily by ____ rather than by anatomic site

tumor morphology

The International Classification of Childhood Cancer (ICCC) groups pediatric cancers into how many main categories?

12 categories

Diffuse midline gliomas have 5-year survival rate of only ____ percent.

4% or 3.80%

The COG ____Committee studies cancers that are ultra-rare or understudied in children and adolescents.

Rare Tumor Committee

Which group of tumors are the leading cause of cancer-related death in children?

Pediatric central nervous system (CNS) tumors

After a new cancer drug receives FDA approval for adults, it can take as long as ____ before it becomes available for pediatric use.

10 years

What is the definition of cancer disparities?

Adverse differences in cancer-related measures that exist among certain population groups.

A national study found that non-Hispanic Black (NHB) individuals were ___% more likely to die from their cancer than non-Hispanic White (NHW) children and adolescents.

28%

Social Drivers of Health (SDOH)

The social, economic and physical conditions in the places where people live, learn, work, play and age that can affect their health

Children residing in rural areas are nearly ____% more likely to die from their cancer than those living in urban areas.

20%

Financial toxicity

The financial problems a patient and their family experience related to the cost of medical care

A 2017 estimate placed the total economic cost of childhood cancer in the US at approximately ____ per patient, combining hospital costs and parental loss of wages

$833,000

What measure of health outcomes combines years of life lost due to premature mortality with years lived with disability?

Disability-adjusted life years (DALYs)

Globally, every $1 invested in pediatric cancer research is projected to yield a return of _____ in productivity gains.

$3

Which piece of federal legislation required companies to evaluate their adult cancer drugs in children if the molecular target is relevant to a pediatric cancer?

The RACE (Research to Accelerate Cures and Equity) for Children Act

The ____ Act allocates $12.6 million each year in genetic sequencing services to pediatric cancers and birth defects

Gabriella Miller Kids First Research Act

What is the primary function of the NCI-sponsored COG biobank initiative, Project: EveryChild?

To gather patient samples (blood, tumor tissues, urine) from all types of pediatric cancer to advance the development of targeted therapies

What is the estimated number of children and adolescents who will be diagnosed with cancer in the US in 2025?

An estimated 14,690