Integrated genomic analysis reveals aberrations in WNT signaling in germ cell tumours of childhood and adolescence

Xu, Luping; Pierce, Joshua L.; Sánchez, Antonio; Chen, K.S.; Shukla, Abhay A.; Fustino, Nicholas J.; Stuart, Sarai H.; Bagrodia, Aditya; Krailo, Mark; Shaikh, Furquan; Billmire, Deborah F.; Pashankar, Farzana; Bestrashniy, Jessica; Oosterhuis, J. Wolter; Biermann, Katharina; Gillis, Ad J. M.; Stoop, J.A.; Xie, Yufang; Teot, Lisa A.; Móra, Josefina; Poynter, Jenny N.; Rakheja, Dinesh; Looijenga, L.H.J.; Draper, Bruce W.; Frazier, A. Lindsay; Amatruda, James F.

doi:10.1016/s1569-9056(19)32491-1

Cited by 2 publications

(8 citation statements)

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“…Patients whose tumors had five or more changes in the WNT pathway had higher beta‐catenin expression and lower EFS and OS. These findings were validated in a separate testicular GCT dataset 24 . The WNT pathway inhibitor tegavivint is being tested in a phase 1/2 study of children and AYA with recurrent or refractory solid tumors including GCTs with WNT pathway aberrations [NCT04851119].…”

Section: Major Findingsmentioning

confidence: 94%

“…A recent study found a mutation rate of 0.23 non-silent mutations/Mb in both type I and II GCTs. 24 Common genomic alteration in GCTs are primarily chromosomal gains/losses and activating mutations in cancer-related genes. Type I tumors show recurrent gains in 12p, 20q, and 21 with losses in 1p and 6q, while type II have gains in 12p (commonly isochromosome i12p).…”

Section: Molecular Targetsmentioning

confidence: 99%

“…These findings were validated in a separate testicular GCT dataset. 24 The WNT pathway inhibitor tegavivint is being tested in a phase 1/2 study of children and AYA with recurrent or refractory solid tumors including GCTs with WNT pathway aberrations…”

Section: Biological Achievementsmentioning

confidence: 99%

“…Similar to many tumors of embryonic origin, GCTs have low mutational burden. A recent study found a mutation rate of 0.23 non‐silent mutations/Mb in both type I and II GCTs 24 . Common genomic alteration in GCTs are primarily chromosomal gains/losses and activating mutations in cancer‐related genes.…”

Section: State Of the Disease: Biologicalmentioning

confidence: 99%

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Children's Oncology Group's 2023 blueprint for research: Germ cell tumors

Bhuta

Shah

Gell

et al. 2023

Pediatric Blood & Cancer

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Extracranial germ cell tumors (GCT) are a biologically diverse group of tumors occurring in children, adolescents, and young adults. The majority of patients have excellent outcomes, but treatment‐related toxicities impact their quality of survivorship. A subset of patients succumbs to the disease. Current unmet needs include clarifying which patients can be safely observed after initial surgical resection, refinement of risk stratification to reduce chemotherapy burden in patients with standard‐risk disease, and intensify therapy for patients with poor‐risk disease. Furthermore, enhancing strategies for detection of minimal residual disease and early detection of relapse, particularly in serum tumor marker‐negative histologies, is critical. Improving the understanding of the developmental and molecular origins of GCTs may facilitate discovery of novel targets. Future efforts should be directed toward assessing novel therapies in a biology‐driven, biomarker‐defined, histology‐specific, risk‐stratified patient population. Fragmentation of care between subspecialists restricts the unified study of these rare tumors. It is imperative that trials be conducted in collaboration with national and international cooperative groups, with harmonized data and biospecimen collection. Key priorities for the Children's Oncology Group (COG) GCT Committee include (a) better understanding the biology of GCTs, with a focus on molecular targets and mechanisms of treatment resistance; (b) strategic development of pediatric and young adult clinical trials; (c) understanding late effects of therapy and identifying individuals most at risk; and (d) prioritizing diversity, equity, and inclusion to reduce cancer health disparities and studying the impacts of social determinants of health on outcomes.

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Section: Major Findingsmentioning

confidence: 94%

Section: Molecular Targetsmentioning

confidence: 99%

Section: Biological Achievementsmentioning

confidence: 99%

Section: State Of the Disease: Biologicalmentioning

confidence: 99%

See 2 more Smart Citations

Children's Oncology Group's 2023 blueprint for research: Germ cell tumors

Bhuta

Shah

Gell

et al. 2023

Pediatric Blood & Cancer

View full text Add to dashboard Cite

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“…We also quantified the association between Klinefelter syndrome and risk of GCT, 14 evaluated the role of predicted leukocyte telomere length in GCT risk, 15 and reported on the higher prevalence of birth defects in GCT cases. Finally, tumor methylation data were used to describe patterns of methylation by tumor histology 16 and to describe aberrations in WNT signaling and their potential role in predicting outcomes 17 . Of note, in collaboration with the COG Outcomes and Survivorship Committee, the GaMETES study has been used to establish a new survivorship cohort to study outcomes and late effects of children and adolescent survivors of GCT 18 .…”

Section: Key Achievementsmentioning

confidence: 99%

Children's Oncology Group's 2023 blueprint for research: Epidemiology

Lupo

Marcotte

Scheurer

et al. 2023

Pediatric Blood & Cancer

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The Children's Oncology Group (COG) Epidemiology Committee has a primary focus on better understanding the etiologies of childhood cancers. Over the past 10 years, the committee has leveraged the Childhood Cancer Research Network, and now more recently Project:EveryChild (PEC), to conduct epidemiologic assessments of various childhood cancers, including osteosarcoma, neuroblastoma, germ cell tumors, Ewing sarcoma, rhabdomyosarcoma, and Langerhans cell histiocytosis. More recent studies have utilized questionnaire data collected as part of PEC to focus on specific characteristics and/or features, including the presence of congenital disorders and the availability of stored cord blood. Members of the COG Epidemiology Committee have also been involved in other large‐scale National Institutes of Health efforts, including the Childhood Cancer Data Initiative and the Gabriella Miller Kids First Pediatric Research Program, which are improving our understanding of the factors associated with childhood cancer risk. Future plans will focus on addressing questions surrounding health disparities, utilizing novel biospecimens in COG epidemiology studies, exploring the role of environmental factors on the etiologies and outcomes of childhood cancer, collaborating with other COG committees to expand the role of epidemiology in childhood cancer research, and building new epidemiologic studies from the Molecular Characterization Initiative—all with the ultimate goal of developing novel prevention and intervention strategies for childhood cancer.

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Integrated genomic analysis reveals aberrations in WNT signaling in germ cell tumours of childhood and adolescence

Cited by 2 publications

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Children's Oncology Group's 2023 blueprint for research: Germ cell tumors

Children's Oncology Group's 2023 blueprint for research: Germ cell tumors

Children's Oncology Group's 2023 blueprint for research: Epidemiology

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