METHODS: A discovery cohort of Malaysian Chinese descent (NPC patients, n = 140; Healthy controls, n = 256) were genotyped using Illumina® HumanOmniExpress BeadChip. PennCNV and cnvPartition calling algorithms were applied for CNV calling. Taqman CNV assays and digital PCR were used to validate CNV calls and replicate candidate copy number variant region (CNVR) associations in a follow-up Malaysian Chinese (NPC cases, n = 465; and Healthy controls, n = 677) and Malay cohort (NPC cases, n = 114; Healthy controls, n = 124).
RESULTS: Six putative CNVRs overlapping GRM5, MICA/HCP5/HCG26, LILRB3/LILRA6, DPY19L2, RNase3/RNase2 and GOLPH3 genes were jointly identified by PennCNV and cnvPartition. CNVs overlapping GRM5 and MICA/HCP5/HCG26 were subjected to further validation by Taqman CNV assays and digital PCR. Combined analysis in Malaysian Chinese cohort revealed a strong association at CNVR on chromosome 11q14.3 (Pcombined = 1.54x10-5; odds ratio (OR) = 7.27; 95% CI = 2.96-17.88) overlapping GRM5 and a suggestive association at CNVR on chromosome 6p21.3 (Pcombined = 1.29x10-3; OR = 4.21; 95% CI = 1.75-10.11) overlapping MICA/HCP5/HCG26 genes.
CONCLUSION: Our results demonstrated the association of CNVs towards NPC susceptibility, implicating a possible role of CNVs in NPC development.
CASE REPORT: Her peripheral smear and bone marrow aspirate showed many myeloblasts. Chromosomal study revealed t(8;22;21)(q22;q12;q22) and loss of X chromosome. Fluorescence in situ hybridization (FISH) using whole chromosome painting probes confirmed the three-way translocation involving chromosomes 8, 21 and 22. RUNX1-RUNX1T1 rearrangement was identified in FISH and reverse transcriptase polymerase chain reaction confirming the diagnosis of AML with variant t(8;21). The patient was treated with standard chemotherapy. She achieved morphological remission one month after induction chemotherapy.
DISCUSSION: Although the clinical significance of variant t(8;21) is not well delineated, the evaluation of 31 such cases suggests patients with variant t(8;21) have similar prognosis to those with classical t(8;21).