A genome-wide assessment of Langerhans Cell Histiocytosis relapse
Purpose: Langerhans Cell Histiocytosis (LCH) is a rare histiocytic disease marked by the aberrant multiplication and accumulation of Langerhans cells. It can occur in various forms thus challenging the established treatment regimen. To make it worse, nearly half of the children suffering from LCH, experience a relapse event. We conducted a GWAS on LCH relapse for the first time with the aim of assessing any genetic susceptibility of experiencing relapse events among children with LCH. ^ Methods: We genotyped a total of 117 LCH patients who were treated at Texas Children’s Cancer Center (TXCH) in Houston, Texas using the Illumina Omni-5 Quad BeadChip. The patients were divided into cases (52, 44%) and controls (65, 66%). We ran a GWAS and compared the SNP frequencies between cases (LCH patients who relapsed) and controls (LCH patients who never relapsed).^ Results: Our study found 12 SNPs suggestive of association and a large number of them were located on chromosome 9. The most significant SNPs rs2182640 (OR=0.16; 0.07-0.35), rs2148702 (OR=0.16; 0.07-0.35), rs1536479 (OR=0.17; 0.08-0.38) and rs3118576 (OR=0.17; 0.08-0.38) located within LOC100506532 (chromosome 9) and rs73221129 (OR=0.30; 0.16-0.56) within PCGF3 (chromosome 4) indicated a protective effect on LCH relapse susceptibility. Other important SNPs were rs4890950 (OR=0.27; 0.14-0.54) and rs1399663 (OR=0.29; 0.15-0.54) on chromosome 18 and rs732119 (KANK1 ) (OR=7.62; 2.65-21.88) on chromosome 9.^ Conclusion: Further research should be done on the important genetic regions found in our GWAS such as LOC100506532 and PCGF3.^
Ghosh, Kankana, "A genome-wide assessment of Langerhans Cell Histiocytosis relapse" (2016). Texas Medical Center Dissertations (via ProQuest). AAI10182177.