Cyclin D2 gene variance and expression level in pediatric acute lymphoblastic leukemia.

BACKGROUND: Cyclin D2 (CCND2) is a crucial player in cell cycle regulation. CCND2 polymorphisms contribute to cancer predisposition. OBJECTIVES: To evaluate the association of CCND2 rs3217927 single nucleotide polymorphisms (SNP) and its expression levels with acute lymphoblastic leukemia (ALL) susceptibility in Egyptian children and its potential prognostic role. METHODS: The 5' nuclease allelic discrimination assay was used to evaluate the frequency of CCND2 rs3217927 SNP in 80 newly diagnosed children with ALL and 80 age- and sex-matched controls. CCND2 relative expression levels were determined by real-time quantitative polymerase chain reaction. RESULTS: The genotype analysis revealed that the GG genotype and G allele were significantly more prevalent among ALL patients than controls (p Ë‚ .001). Regression analysis demonstrated that Egyptian children carrying only one G allele had about 31-fold increased risk to develop ALL compared to A allele carriers. CCND2 was overexpressed in ALL patients compared to controls (p < .001). The CCND2 overexpression was associated with the GG genotype and G allele (p < .001). Furthermore, G allele was an independent negative prognostic marker for central nervous system (CNS) involvement (odds ratio [OR] = 4.676; 95% confidence interval [CI]: 1.2-18.6), risk stratification (OR = 38; 95% CI: 7.7-188.2), and chemoresistance (OR = 9.864; 95% CI: 5.6-70.3) in ALL patients. CONCLUSIONS: G allele of CCND2 rs3217927 SNP might be associated with increased risk for ALL in Egyptian children besides being an independent negative prognostic marker for their risk stratification and therapeutic outcome. CCND2 rs3217927 SNP genotyping might be used to demarcate ALL patients with aggressive disease phenotypes who may be candidate for alternative targeted therapeutic strategies.

Evaluation of saccular and inferior vestibular nerve function in children with auditory neuropathy spectrum disorder.

PURPOSE: The aim of the current work was to evaluate the function of the saccule and inferior vestibular nerve in children with auditory neuropathy spectrum disorder (ANSD) by recording the cervical-evoked myogenic potentials (C-VEMP) on those children and to compare C-VEMP results in ANSD children of pre-lingual onset to those in ANSD children of post-lingual onset. METHODS: The study included 38 ANSD children of pre-lingual onset, 16 ANSD children of post-lingual onset, and 20 control children. All participant children were subjected to C-VEMP testing using 500 Hz tone burst stimuli. RESULTS: The vast majority of ANSD children of pre-lingual onset (35 out of 38; 92.1%) had bilateral intact C-VEMP response with C-VEMP parameters (amplitude, asymmetric ratio, latency, and inter-aural latency difference) that were not statistically different than those in the control children. Only three children had bilateral absent C-VEMP response. On the other hand, the majority of ANSD children of post-lingual onset (11 out of 16; 68.75%) had bilateral absent C-VEMP response. The remaining five children had bilateral intact C-VEMP response with C-VEMP parameters that were not statistically different than those in the control children. CONCLUSIONS: The pathology of ANSD spares the saccule and inferior vestibular nerve in the vast majority of ANSD children of pre-lingual onset, while it involves them in the majority of ANSD of post-lingual onset reflecting different site(s) of lesion between the two ANSD categories. Such results have important clinical implications as regards to the management of ANSD in children.