Genetic Variation Tied to Childhood ALL, Poor Outcomes

Carrying germline variants linked to decreased event-free, overall survival; higher risk of second cancers
Carrying germline variants linked to decreased event-free, overall survival; higher risk of second cancers

HealthDay News — TP53 pathogenic variants are overrepresented in children with acute lymphoblastic leukemia (ALL) and are associated with worse outcomes, according to a study published online January 4 in the Journal of Clinical Oncology.

Maoxiang Qian, PhD, from St. Jude Children's Research Hospital in Memphis, Tennessee, and colleagues performed targeted sequencing of TP53 coding regions in 3,801 children from ALL clinical trials to examine the pattern, prevalence, and clinical relevance of TP53 variants in childhood ALL. 

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The researchers identified 49 unique non-silent rare TP53 coding variants in 77 of the patients sequenced (2%); 22 of the variants were classified as pathogenic. Compared with non-ALL controls, in ALL, TP53 pathogenic variants were significantly over represented (odds ratio, 5.2). The presence of TP53 pathogenic variants was associated with significantly older age at diagnosis (median age, 15.5 versus 7.3) and increased likelihood of having hypodiploid ALL (65.4 versus 1.2%). Inferior event-free and overall survival were seen in association with carrying germline TP53 pathogenic variants (hazard ratios, 4.2 and 3.9, respectively). Compared to children without pathogenic variants, children with pathogenic variants had a higher risk of second cancers (5-year cumulative incidence, 25.1 versus 0.7%).

"Loss-of-function germline TP53 variants predispose children to ALL and to adverse treatment outcomes of ALL therapy, particularly the risk of second malignant neoplasms," the authors write.

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