Identification of Familial Hodgkin Lymphoma Predisposing Genes Using Whole Genome Sequencing

MedRxiv : the Preprint Server for Health Sciences
Aayushi SrivastavaObul Reddy Bandapalli

Abstract

Hodgkin lymphoma (HL) is a lymphoproliferative malignancy of B-cell origin that accounts for 10% of all lymphomas. Despite evidence suggesting strong familial clustering of HL, there is no clear understanding of the contribution of genes predisposing to HL. In this study, whole genome sequencing (WGS) was performed on 7 affected and 9 unaffected family members from three HL-prone families and variants were prioritized using our Familial Cancer Variant Prioritization Pipeline (FCVPPv2). WGS identified a total of 98564, 170550 and 113654 variants which were reduced by pedigree-based filtering to 18158, 465 and 26465 in families I, II and III, respectively. In addition to variants affecting amino acid sequences, variants in promoters, enhancers, transcription factors binding sites and microRNA seed sequences were identified from upstream, downstream, 5 and 3 prime untranslated regions. A panel of 565 cancer predisposing and other cancer-related genes and of 2383 high-risk HL genes were also screened in these families to aid further prioritization. Pathway analysis of segregating genes with CADD (Combined Annotation Dependent Depletion Tool) scores > 20 was performed using Ingenuity Pathway Analysis software which implicated severa...Continue Reading

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