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Single nucleotide p...
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
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Mougeot, Jean-Luc C. (author)
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Beckman, Micaela F. (author)
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Alexander, Adam S. (author)
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Hovan, Allan J. (author)
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- Hasséus, Bengt, 1955 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för odontologi,Institute of Odontology
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Legert, Karin Garming (author)
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Johansson, Jan-Erik (author)
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- von Bültzingslöwen, Inger, 1947 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för odontologi,Institute of Odontology
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Brennan, Michael T. (author)
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Mougeot, Farah Bahrani (author)
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(creator_code:org_t)
- 2024
- 2024
- English.
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In: SUPPORTIVE CARE IN CANCER. - 0941-4355 .- 1433-7339. ; 32:4
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Abstract
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- PurposeLeukemias 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).MethodsWhole 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.ResultsIn 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."ConclusionsWe identified candidate SNPs possibly conferring susceptibility to develop leukemia and oral mucositis.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Keyword
- Leukemia
- Non-cancer blood disorders
- Oral mucositis
- Whole exome sequencing
- Single nucleotide polymorphism
Publication and Content Type
- ref (subject category)
- art (subject category)
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Mougeot, Jean-Lu ...
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Beckman, Micaela ...
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Alexander, Adam ...
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Hovan, Allan J.
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Hasséus, Bengt, ...
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Legert, Karin Ga ...
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show more...
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Johansson, Jan-E ...
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von Bültzingslöw ...
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Brennan, Michael ...
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Mougeot, Farah B ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
- Articles in the publication
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SUPPORTIVE CARE ...
- By the university
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University of Gothenburg
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Karolinska Institutet