NDLI: Epigenome-wide analysis across the development span of pediatric acute lymphoblastic leukemia: backtracking to birth

Content Provider	Springer Nature : BioMed Central
Author	Ghantous, Akram Nusslé, Semira Gonseth Nassar, Farah J. Spitz, Natalia Novoloaca, Alexei Krali, Olga Nickels, Eric Cahais, Vincent Cuenin, Cyrille Roy, Ritu Li, Shaobo Caron, Maxime Lam, Dilys Fransquet, Peter Daniel Casement, John Strathdee, Gordon Pearce, Mark S. Hansen, Helen M. Lee, Hwi-Ho Lee, Yong Sun de Smith, Adam J. Sinnett, Daniel Håberg, Siri Eldevik McKay, Jill A. Nordlund, Jessica Magnus, Per Dwyer, Terence Saffery, Richard Wiemels, Joseph Leo Munthe-Kaas, Monica Cheng Herceg, Zdenko
Abstract	Background Cancer is the leading cause of disease-related mortality in children. Causes of leukemia, the most common form, are largely unknown. Growing evidence points to an origin in-utero, when global redistribution of DNA methylation occurs driving tissue differentiation. Methods Epigenome-wide DNA methylation was profiled in surrogate (blood) and target (bone marrow) tissues at birth, diagnosis, remission and relapse of pediatric pre-B acute lymphoblastic leukemia (pre-B ALL) patients. Double-blinded analyses was performed between prospective cohorts extending from birth to diagnosis and retrospective studies backtracking from clinical disease to birth. Validation was carried out using independent technologies and populations. Results The imprinted and immuno-modulating VTRNA2-1 was hypermethylated (FDR<0.05) at birth in nested cases relative to controls in all tested populations (totaling 317 cases and 483 controls), including European and Hispanic ancestries. VTRNA2-1 methylation was stable over follow-up years after birth and across surrogate, target and other tissues (n=5,023 tissues; 30 types). When profiled in leukemic tissues from two clinical cohorts (totaling 644 cases), VTRNA2-1 methylation exhibited higher levels at diagnosis relative to controls, it reset back to normal levels at remission, and then re-increased to above control levels at relapse. Hypermethylation was significantly associated with worse pre-B ALL patient survival and with reduced VTRNA2-1 expression (n=2,294 tissues; 26 types), supporting a functional and translational role for VTRNA2-1 methylation. Conclusion This study provides proof-of-concept to detect at birth epigenetic precursors of pediatric pre-B ALL. These alterations were reproducible with different technologies, in three continents and in two ethnicities, and can offer biomarkers for early detection and prognosis as well as actionable targets for therapy.
Related Links	https://molecular-cancer.biomedcentral.com/counter/pdf/10.1186/s12943-024-02118-4.pdf
Ending Page	8
Page Count	8
Starting Page	1
File Format	HTM / HTML
ISSN	14764598
DOI	10.1186/s12943-024-02118-4
Journal	Molecular Cancer
Issue Number	1
Volume Number	23
Language	English
Publisher	BioMed Central
Publisher Date	2024-10-23
Access Restriction	Open
Subject Keyword	Cancer Research Oncology VTRNA2-1 Pediatric leukemia Epigenetics DNA methylation Birth cohort Neonatal blood spots
Content Type	Text
Resource Type	Correspondence
Subject	Oncology Molecular Medicine Cancer Research
Journal Impact Factor	27.7/2023
5-Year Journal Impact Factor	31.3/2023

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Commentary on “Epigenome-wide analysis across the development span of pediatric acute lymphoblastic leukemia: backtracking to birth”

Periconceptional folate intake influences DNA methylation at birth based on dietary source in an analysis of pediatric acute lymphoblastic leukemia cases and controls

DNA methylation-based subtype prediction for pediatric acute lymphoblastic leukemia

Transcriptome sequencing in pediatric acute lymphoblastic leukemia identifies fusion genes associated with distinct DNA methylation profiles

Genome-wide signatures of differential DNA methylation in pediatric acute lymphoblastic leukemia

Refining risk prediction in pediatric acute lymphoblastic leukemia through DNA methylation profiling

Genome-wide signatures of differential DNA methylation in pediatric acute lymphoblastic leukemia

DNA Methylation in Ovarian Cancer Susceptibility

DNA Methylation Signatures Predict Cytogenetic Subtype and Outcome in Pediatric Acute Myeloid Leukemia (AML)

Epigenome-wide analysis across the development span of pediatric acute lymphoblastic leukemia: backtracking to birth

Similar Documents

Commentary on “Epigenome-wide analysis across the development span of pediatric acute lymphoblastic leukemia: backtracking to birth”

Periconceptional folate intake influences DNA methylation at birth based on dietary source in an analysis of pediatric acute lymphoblastic leukemia cases and controls

DNA methylation-based subtype prediction for pediatric acute lymphoblastic leukemia

Transcriptome sequencing in pediatric acute lymphoblastic leukemia identifies fusion genes associated with distinct DNA methylation profiles

Genome-wide signatures of differential DNA methylation in pediatric acute lymphoblastic leukemia

Refining risk prediction in pediatric acute lymphoblastic leukemia through DNA methylation profiling

Genome-wide signatures of differential DNA methylation in pediatric acute lymphoblastic leukemia

DNA Methylation in Ovarian Cancer Susceptibility

DNA Methylation Signatures Predict Cytogenetic Subtype and Outcome in Pediatric Acute Myeloid Leukemia (AML)

Epigenome-wide analysis across the development span of pediatric acute lymphoblastic leukemia: backtracking to birth