Novel Susceptibility Variants at 10p12.31-12.2 for Childhood Acute Lymphoblastic Leukemia in Ethnically Diverse Populations

Xu, Hong‐Xi; Yang, Wenjian; Pérez-Andreu, Virginia; Devidas, Meenakshi; Fan, Yiping; Cheng, Cheng; Pei, Deqing; Scheet, Paul; Burchard, Esteban G.; Eng, Celeste; Huntsman, Scott; Torgerson, Dara G.; Dean, Michael; Winick, Naomi J.; Martin, Paul L.; Camitta, Bruce M.; Bowman, W. Paul; Willman, Cheryl L.; Carroll, William L.; Mullighan, Charles G.; Bhojwani, Deepa; Hunger, Stephen P.; Pui, Ching Hon; Evans, William E.; Relling, Mary V.; Loh, Mignon L.; Yang, Jun J.

doi:10.1093/jnci/djt042

Cited by 205 publications

(261 citation statements)

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“…Most GWAS, until recently, have identified risk loci using only European-origin populations. Variant polymorphisms located within the ARID5B, IKZF1, and CEBPE genes have reported strong risk associations in multiple studies [19][20][21][22][38][39][40]. Our study provides some confirmation of previously discovered genetic markers associated with childhood ALL, which also validated our case-control set for further exploration.…”

Section: Discussionsupporting

confidence: 81%

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Genetic markers in a multi-ethnic sample for childhood acute lymphoblastic leukemia risk

Kennedy¹,

Kamdar²,

Lupo³

et al. 2014

Leukemia & Lymphoma

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Genome-wide association studies have identified multiple risk loci for childhood acute lymphoblastic leukemia (ALL), but mostly in European/White populations despite Hispanics having a greater risk. We re-examined SNPs of known associations with childhood ALL and known HLA region lymphoma risk markers in a multi-ethnic population. Significant associations were found in two ARID5B variants (rs7089424 and rs10821936). We replicated a strong risk association in non-Hispanic White males with rs2395185, a protective marker for lymphoma.Another HLA region marker, rs2647012, showed a risk association among Hispanics only, while a strong protective association was found with rs1048456, a follicular lymphoma risk marker.Our study validated this new case-control sample by confirming genetic markers associated with childhood ALL, and yielded new associations with lymphoma markers. Despite positive results, our study did not provide any clues to why Hispanics have a higher susceptibility to childhood leukemia, suggesting that environmental factors may have a strong contribution.

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Section: Discussionsupporting

confidence: 81%

“…Genome-wide association studies (GWAS) [19][20][21][22] American populations [8,22], discovering that some markers are universal across races/ethnicities, while others are race/ethnic-specific.…”

Section: Introductionmentioning

confidence: 99%

Genetic markers in a multi-ethnic sample for childhood acute lymphoblastic leukemia risk

Kennedy¹,

Kamdar²,

Lupo³

et al. 2014

Leukemia & Lymphoma

View full text Add to dashboard Cite

show abstract

“…[86][87][88][89][90] Associations with specific ALL subtypes and relapse have also been identified. [91][92][93][94][95] Several genes such as IKZF1, CEBPE, and GATA3 encode transcription factors that are also targets of somatic genetic alteration in ALL.…”

Section: Inherited Genetic Variation and All Risk And Outcomementioning

confidence: 99%

Redefining ALL classification: toward detecting high-risk ALL and implementing precision medicine

Hunger

Mullighan

2015

Blood

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237

198

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Acute lymphoblastic leukemia (ALL) is the commonest childhood tumor and remains a leading cause of cancer death in the young. In the last decade, microarray and sequencing analysis of large ALL cohorts has revolutionized our understanding of the genetic basis of this disease. These studies have identified new ALL subtypes, each characterized by constellations of structural and sequence alterations that perturb key cellular pathways, including lymphoid development, cell-cycle regulation, and tumor suppression; cytokine receptor, kinase, and Ras signaling; and chromatin modifications. Several of these pathways, particularly kinase-activating lesions and epigenetic alterations, are logical targets for new precision medicine therapies. Genomic profiling has also identified important interactions between inherited genetic variants that influence the risk of leukemia development and the somatic genetic alterations that are required to establish the leukemic clone. Moreover, sequential sequencing studies at diagnosis, remission, and relapse have provided important insights into the relationship among genetic variants, clonal heterogeneity, and the risk of relapse. Ongoing studies are extending our understanding of coding and noncoding genetic alterations in B-progenitor and T-lineage ALL and using these insights to inform the development of faithful experimental models to test the efficacy of new treatment approaches. (Blood. 2015;125(26):3977-3987)

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“…In the largest study of inherited risk genes so far, published in March 2013, his team scanned the genomes of 2,450 children with ALL and 10,977 controls 6 .…”

Section: Inherited Riskmentioning

confidence: 99%

Genetics: Written in blood

DeWeerdt¹

2013

Nature

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Novel Susceptibility Variants at 10p12.31-12.2 for Childhood Acute Lymphoblastic Leukemia in Ethnically Diverse Populations

Abstract: These findings indicate strong associations between inherited genetic variation and ALL susceptibility in children and shed new light on ALL molecular etiology in diverse ancestry.

Cited by 205 publications

References 50 publications

Genetic markers in a multi-ethnic sample for childhood acute lymphoblastic leukemia risk

Genetic markers in a multi-ethnic sample for childhood acute lymphoblastic leukemia risk

Redefining ALL classification: toward detecting high-risk ALL and implementing precision medicine

Genetics: Written in blood

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