单核苷酸多态性与白血病和口腔黏膜炎易感性的关系：造血干细胞移植预处理患者的多中心先导研究。

Single nucleotide polymorphisms conferring susceptibility to leukemia and oral mucositis: a multi-center pilot study of patients prior to conditioning therapy for hematopoietic cell transplant.

机构信息

Translational Research Laboratories, Department of Oral Medicine/Oral & Maxillofacial Surgery, Atrium Health Carolinas Medical Center, Charlotte, NC, USA.

Department of Otolaryngology/Head & Neck Surgery, Wake Forest University School of Medicine, Winston-Salem, NC, USA.

出版信息

Support Care Cancer. 2024 Mar 11;32(4):220. doi: 10.1007/s00520-024-08408-3.

DOI:10.1007/s00520-024-08408-3

PMID:38467943

Abstract

PURPOSE

Leukemias have been associated with oral manifestations, reflecting susceptibility to cancer therapy-induced oral mucositis. We sought to identify SNPs associated with both leukemia and oral mucositis (OM).

METHODS

Whole exome sequencing was performed on leukemia and non-cancer blood disorder (ncBD) patients' saliva samples (N = 50) prior to conditioning therapy. WHO OM grading scores were determined: moderate to severe (OM2-4) vs. none to mild (OM0-1). Reads were processed using Trim Galorev0.6.7, Bowtie2v2.4.1, Samtoolsv1.10, Genome Analysis Toolkit (GATK)v4.2.6.1, and DeepVariantv1.4.0. We utilized the following pipelines: P1 analysis with PLINK2v3.7, SNP2GENEv1.4.1 and MAGMAv1.07b, and P2 [leukemia (N = 42) vs. ncBDs (N = 8)] and P3 [leukemia + OM2-4 (N = 18) vs. leukemia + OM0-1 (N = 24)] with Z-tests of genotypes and protein-protein interaction determination. GeneCardsSuitev5.14 was used to identify phenotypes (P1 and P2, leukemia; P3, oral mucositis) and average disease-causing likelihood and DGIdb for drug interactions. P1 and P2 genes were analyzed with CytoScape plugin BiNGOv3.0.3 to retrieve overrepresented Gene Ontology (GO) terms and Ensembl's VEP for SNP outcomes.

RESULTS

In P1, 457 candidate SNPs (28 genes) were identified and 21,604 SNPs (1016 genes) by MAGMAv1.07b. Eighteen genes were associated with "leukemia" per VarElectv5.14 analysis and predicted to be deleterious. In P2 and P3, 353 and 174 SNPs were significant, respectively. STRINGv12.0 returned 77 and 32 genes (C.L. = 0.7) for P2 and P3, respectively. VarElectv5.14 determined 60 genes from P2 associated with "leukemia" and 11 with "oral mucositis" from P3. Overrepresented GO terms included "cellular process," "signaling," "hemopoiesis," and "regulation of immune response."

CONCLUSIONS

We identified candidate SNPs possibly conferring susceptibility to develop leukemia and oral mucositis.

摘要

目的

白血病与口腔表现有关，反映了对癌症治疗诱导的口腔粘膜炎的易感性。我们试图确定与白血病和口腔粘膜炎（OM）均相关的单核苷酸多态性（SNP）。

方法

在进行调理治疗前，对白血病和非癌症血液疾病（ncBD）患者的唾液样本（N=50）进行全外显子测序。根据世界卫生组织（WHO）口腔粘膜炎分级评分确定：中重度（OM2-4）与无或轻度（OM0-1）。使用 Trim Galore v0.6.7、Bowtie2 v2.4.1、Samtools v1.10、基因组分析工具包（GATK）v4.2.6.1 和 DeepVariant v1.4.0. 处理读数。我们利用了以下分析方法：P1 分析使用 PLINK2 v3.7、SNP2GENE v1.4.1 和 MAGMA v1.07b，P2 [白血病（N=42）与 ncBDs（N=8）]和 P3 [白血病+OM2-4（N=18）与白血病+OM0-1（N=24）]使用基因型的 Z 检验和蛋白质-蛋白质相互作用的确定。使用 GeneCardsSuite v5.14 识别表型（P1 和 P2，白血病；P3，口腔粘膜炎）和平均致病可能性以及 DGIdb 以确定药物相互作用。使用 CytoScape 插件 BiNGO v3.0.3 分析 P1 和 P2 基因，以检索过代表的基因本体论（GO）术语和 Ensembl 的 SNP 结果的 VEP。

结果

在 P1 中，通过 MAGMA v1.07b 鉴定了 457 个候选 SNP（28 个基因）和 21604 个 SNP（1016 个基因）。通过 VarElect v5.14 分析，18 个基因与“白血病”相关，并预测为有害。在 P2 和 P3 中，分别有 353 个和 174 个 SNP 是显著的。STRING v12.0 分别为 P2 和 P3 返回 77 个和 32 个基因（C.L. = 0.7）。通过 VarElect v5.14 确定了 P2 中与“白血病”相关的 60 个基因，以及 P3 中与“口腔粘膜炎”相关的 11 个基因。过代表的 GO 术语包括“细胞过程”、“信号”、“造血”和“免疫反应调节”。